The patient acceptability of a remotely delivered pain management programme for people with persistent musculoskeletal pain: A qualitative evaluation.

Introduction: Remotely delivered pain management programmes have been offered in place of in-person programmes by many chronic pain services since the onset of the COVID-19 pandemic. There is a lack of evidence regarding the acceptability of these programmes. In this evaluation, we have explored patients' acceptability of a remotely delivered pain management programme for patients with persistent musculoskeletal pain. Methods: Qualitative data were collected using focus groups with participants who had previously attended the remote pain management programme. Data were analysed using abductive analysis. Results: Three focus groups were conducted with a total of 13 participants. The programmme was either entirely acceptable, had some acceptable components or was not acceptable to patients. Factors leading to the programme being acceptable include learning to manage pain from home, receiving high quality care from home, enhancing the potential of rehabilitation using technology, enabling attendance on a pain management programme from home, overcoming social distancing requirements of COVID-19 using technology, and virtual peer support. Factors leading to the programme not being acceptable include having an inappropriate home environment for virtual therapy, communication challenges with virtual therapy, technological issues and concerns regarding the quality of care. Conclusions: There is a spectrum of acceptability with respect to the remote programme. The factors that influence this are dynamic, individual and situational. Hybrid programmes have the potential to enhance access to pain management programmes and improve patient experience and programme outcomes in the future.

Transmembrane peptide effects on bacterial membrane integrity and organization.

As the bacterial multidrug resistance crisis continues, membrane-active antimicrobial peptides are being explored as an alternate treatment to conventional antibiotics. In contrast to antimicrobial peptides, which function by a nonspecific membrane disruption mechanism, here we describe a series of transmembrane (TM) peptides that are designed to act as drug efflux inhibitors by aligning with and out-competing a conserved TM4-TM4 homodimerization motif within bacterial small multidrug resistance proteins. The peptides contain two terminal tags: a C-terminal lysine tag to direct the peptides toward the negatively charged bacterial membrane, and an uncharged N-terminal sarcosine (N-methyl-glycine) tag to promote membrane insertion. While effective at inhibiting efflux activity, ostensibly through their designed mechanism of action, the impact of the peptides on the bacterial inner membrane remains undetermined. To evaluate the extant peptide-membrane interactions, we performed a series of biophysical measurements. Circular dichroism spectroscopy and Trp fluorescence showed that the peptides insert into the membrane generally in helical form. Interestingly, differential scanning calorimetry of the peptides added to bacterial-like membranes (POPE:POPG 3:1) revealed the peptides' ability to demix the POPE and POPG lipids, creating two pools, one of which is likely a peptide-POPG conglomerate, and the other a POPE-rich component where the native POPG content has been depleted. However, dye leakage assays confirmed that these events occur without causing significant membrane disruption both in vitro and in vivo, indicating that the peptides can target the small multidrug resistance TM4-TM4 motif without nonspecific membrane disruption. In related studies, DiOC2(3) fluorescence indicated moderate peptide-mediated reduction of the proton motive force for all peptides, including control peptides that did not display inhibitory activity. The overall findings suggest that peptides designed with suitable tags, sequence hydrophobicity, and charge distribution can be directed more generally to impact proteins whose function involves membrane-embedded protein-protein interactions.

Rapid design and implementation of a virtual pain management programme due to COVID-19: a quality improvement initiative.

Background: The COVID-19 pandemic interrupted the delivery of face-to-face pain services including pain management programmes in the United Kingdom with considerable negative impact on patients with chronic musculoskeletal pain. We aimed to develop and implement a remotely delivered pain management programme (PMP) using video-conferencing technology that contains all the core components of a full programme: the 'virtual PMP' (vPMP). By reporting on the process of this development, we endeavour to help address the paucity of literature on the development of remote pain management programmes. Methods: The vPMP was developed by an inter-disciplinary group of professionals as a quality improvement (QI) project. The Model for Improvement Framework was employed with patient involvement at the design phase and at subsequent improvements. Improvement was measured qualitatively with frequent and repeated qualitative data collection leading to programme change. Quantitative patient demographic comparisons were made with a patient cohort who had been on a face-to-face PMP pathway. Results: Sixty-one patients on the PMP waiting list were contacted and 43 met the criteria for the programme. Fourteen patients participated in three vPMP cycles. Patient involvement and comprehensive stakeholder consultation were essential to a robust design for the first vPMP. Continued involvement of patient partners during the QI process led to rapid resolution of implementation problems. The most prominent issues that needed action were technical challenges including training needs, participant access to physical and technological resources, participant fatigue and concerns about adequate communication and peer support. Conclusion: This report demonstrates how a remotely delivered PMP, fully in line with national guidance, was rapidly developed and implemented in a hospital setting for patients with chronic musculoskeletal pain. We also discuss the relevance of our findings to the issues of cost, patient experience, patient preferences and inequities of access in delivering telerehabilitation for chronic pain.

Reactions to messages about smoking, vaping and COVID-19: two national experiments.

INTRODUCTION: The pace and scale of the COVID-19 pandemic, coupled with ongoing efforts by health agencies to communicate harms, have created a pressing need for data to inform messaging about smoking, vaping, and COVID-19. We examined reactions to COVID-19 and traditional health harms messages discouraging smoking and vaping. METHODS: Participants were a national convenience sample of 810 US adults recruited online in May 2020. All participated in a smoking message experiment and a vaping message experiment, presented in a random order. In each experiment, participants viewed one message formatted as a Twitter post. The experiments adopted a 3 (traditional health harms of smoking or vaping: three harms, one harm, absent) × 2 (COVID-19 harms: one harm, absent) between-subjects design. Outcomes included perceived message effectiveness (primary) and constructs from the Tobacco Warnings Model (secondary: attention, negative affect, cognitive elaboration, social interactions). RESULTS: Smoking messages with traditional or COVID-19 harms elicited higher perceived effectiveness for discouraging smoking than control messages without these harms (all p <0.001). However, including both traditional and COVID-19 harms in smoking messages had no benefit beyond including either alone. Smoking messages affected Tobacco Warnings Model constructs and did not elicit more reactance than control messages. Smoking messages also elicited higher perceived effectiveness for discouraging vaping. Including traditional harms in messages about vaping elicited higher perceived effectiveness for discouraging vaping (p <0.05), but including COVID-19 harms did not. CONCLUSIONS: Messages linking smoking with COVID-19 may hold promise for discouraging smoking and may have the added benefit of also discouraging vaping.

HPV vaccine communication training in healthcare systems: Evaluating a train-the-trainer model.

BACKGROUND: Large healthcare systems provide an opportunity to disseminate evidence-based interventions to primary care. We evaluated the impact of a train-the-trainer model in two large systems to disseminate the Announcement Approach Training, which teaches providers to communicate about HPV vaccination more effectively. METHODS: In collaboration with the American Cancer Society, we partnered with two midwestern healthcare systems that served over 77,000 patients ages 11 through 17. Both systems hosted a 2-hour train-the-trainer workshop. Providers from one system then conducted in-person 1-hour CME-eligible trainings, using our standard slide set and script (available at hpvIQ.org). The other system did not implement trainings, providing a natural experiment. RESULTS: The train-the-trainer workshop included physicians, nurses and other clinical staff (n = 11/13 for intervention/comparison systems). The intervention system delivered 18 trainings to 234 physicians, nurses, and other clinic staff. From baseline to 6-month follow-up, the intervention system had an increase in HPV vaccine uptake that was larger than that of the comparison system for adolescents ages 11 through 12 (1.9%, p = .002) and ages 13 through 17 (1.5%, p = .015). Attending the training was associated with increased intentions to routinely recommend HPV vaccine when patients turn 11 or 12 (mean 4.19 (SD = 0.95) vs. 4.43 (SD = 0.83) as well as increased positive vaccine attitudes, self-efficacy, and norms (all p < .001). Participant satisfaction with the trainings was high (90%-94%). CONCLUSION: The train-the-trainer model was effective in increasing provider motivation to recommend HPV vaccination and led to a small increase in vaccine uptake. Dissemination through large healthcare systems is promising but faces some challenges.

Improving young children's handwashing behaviour and understanding of germs: The impact of A Germ's Journey educational resources in schools and public spaces.

CONTEXT: Effective handwashing can prevent the spread of germs, including Covid-19. However, young children can lack a fundamental understanding of germ transfer. A Germ's Journey educational resources were designed to support young children in learning about germs and handwashing. These resources include a book, website, song, online games and glo-gel activities that are informed by a behaviour change model. RESEARCH GAP: Prior research has not evaluated the impacts of these resources on behavioural outcomes. PURPOSE OF THE STUDY: Two intervention studies evaluated the impacts of these resources on both knowledge and behavioural outcomes. METHOD: In Study 1, children (n = 225) were recruited from four schools and randomly assigned by classrooms to participate in a multicomponent intervention (vs. control). In Study 2, children (n = 104) were recruited from a museum and randomly assigned to participate in a song intervention (vs. control). Trained observers recorded participants' engagement in six handwashing behaviours and their understanding of germs. These behavioural and knowledge outcomes were analysed using regression and related analyses. RESULTS: In Study 1, significant improvements were observed between baseline and follow up in the intervention group for both behavioural scores (Est = 0.48, SE = 0.14, t = 3.30, p = 0.001) and knowledge scores (Est = 2.14, SE = 0.52, z = 4.11, p < 0.001), whereas these improvements were not observed in the control group (ts < 1). In Study 2, the intervention group had significantly higher behavioural scores compared to the control group (Est. = -0.71, SE = 0.34, t = -2.07, p = 0.04). CONCLUSION: This research demonstrates that specifically designed hand hygiene educational resources can improve handwashing practice and understanding in young children, and could lead to the reduction of the transmission of disease within this group.

Peptide-Based Approach to Inhibition of the Multidrug Resistance Efflux Pump AcrB.

Clinically relevant multidrug-resistant bacteria often arise due to overproduction of membrane-embedded efflux proteins that are capable of pumping antibiotics out of the bacterial cell before the drugs can exert their intended toxic effect. The Escherichia coli membrane protein AcrB is the archetypal protein utilized for bacterial efflux study because it can extrude a diverse range of antibiotic substrates and has close homologues in many Gram-negative pathogens. Three AcrB subunits, each of which contains 12 transmembrane (TM) helices, are known to trimerize to form the minimal functional unit, stabilized noncovalently by helix-helix interactions between TM1 and TM8. To inhibit the efflux activity of AcrB, we have rationally designed synthetic peptides aimed at destabilizing the AcrB trimerization interface by outcompeting the subunit interaction sites within the membrane. Here we report that peptides mimicking TM1 or TM8, with flanking N-terminal peptoid tags, and C-terminal lysine tags that aid in directing the peptides to their membrane-embedded target, decrease the AcrB-mediated efflux of the fluorescent substrate Nile red and potentiate the effect of the antimicrobials chloramphenicol and ethidium bromide. To further characterize the motif encompassing the interaction between TM1 and TM8, we used Förster resonance energy transfer to demonstrate dimerization. Using the TM1 and TM8 peptides, in conjunction with several selected mutant peptides, we highlight residues that may increase the potency and specificity of the peptide drug candidates. In targeting membrane-embedded protein-protein interactions, this work represents a novel approach to AcrB inhibition and, more broadly, a potential route to a new category of efflux pump inhibitors.

Orally administered emu oil attenuates disease in a mouse model of Crohn's-like colitis.

Crohn's disease is a severe, incurable inflammatory bowel disease. Orally administered emu oil has demonstrated anti-inflammatory properties in previous models of gastrointestinal disease. We aimed to determine whether orally administered emu oil could attenuate disease in a mouse model of Crohn's-like colitis. Female ARC(s) mice (CD-1 equivalent, n = 10/group) were intra-rectally administered water (120 µL) or trinitrobenzene sulfonic acid (TNBS; 3 mg in 50% ethanol; 120 µL bolus) on day 0. Mice were orally administered water (80 µL) or emu oil (80 µL or 160 µL) daily for five days and euthanized on day six. Bodyweight and disease activity were recorded daily. Colonoscopy, burrowing activity, facial grimace, histological parameters (damage severity, small intestinal villus height/crypt depth and colonic crypt depth), myeloperoxidase activity and intestinal permeability were assessed. P < 0.05 was considered statistically significant. TNBS decreased bodyweight (days 1, 2, 4; P < 0.05) and increased disease activity (days 1-6; P < 0.01), compared to normal controls. Emu oil (80 µL) attenuated disease activity on days 5-6 (P < 0.05), although bodyweight loss was not significantly impacted (P > 0.05). Facial grimace and colonoscopy scores were significantly increased in TNBS-control mice; effects attenuated by both volumes of emu oil (P < 0.001). TNBS increased histological damage severity compared to normal controls (P < 0.05); an effect attenuated by 80 µL emu oil (proximal and distal colon; P < 0.05) and 160 µL emu oil (distal colon; P < 0.01). In the ileum, villus height and crypt depth were unaffected by TNBS or emu oil treatment compared to normal (P > 0.05). TNBS-induced distal colonic crypt lengthening was unaffected following emu oil administration (P > 0.05). Remaining parameters, including burrowing, myeloperoxidase activity and intestinal permeability, were unchanged across all treatment groups (P > 0.05). In normal mice, emu oil treatment did not significantly impact any parameter compared to normal controls. In conclusion, emu oil reduced overall disease severity and facial grimace scores in TNBS mice. These results suggest therapeutic potential for orally administered emu oil in the management of Crohn's disease.

Peptide-Based Efflux Pump Inhibitors of the Small Multidrug Resistance Protein from Pseudomonas aeruginosa.

Bacteria have acquired multiple mechanisms to evade the lethal effects of current therapeutics, hindering treatment of bacterial infections, such as those caused by the pathogen Pseudomonas aeruginosa, which is responsible for nosocomial and cystic fibrosis lung infections. One resistance mechanism involves membrane-embedded multidrug efflux pumps that can effectively extrude an array of substrates, including common antibiotics, dyes, and biocides. Among these is a small multidrug resistance (SMR) efflux protein, consisting of four transmembrane (TM) helices, that functions as an antiparallel dimer. TM helices 1 to 3 (TM1 to TM3) comprise the substrate binding pocket, while TM4 contains a GG7 heptad sequence motif that mediates the SMR TM4-TM4 dimerization. In the present work, we synthesized a series of peptides containing the residues centered on the TM4-TM4 binding interface found in the P. aeruginosa SMR (PAsmr), typified by Ac-Ala-(Sar)3-LLGIGLIIAGVLV-KKK-NH2 (helix-helix interaction residues are underlined). Here, the acetylated N-terminal sarcosine (N-methyl-Gly) tag [Ac-Ala-(Sar)3] promotes membrane penetration, while the C-terminal Lys tag promotes selectivity for the negatively charged bacterial membranes. This peptide was observed to competitively disrupt PAsmr-mediated efflux, as measured by efflux inhibition of the fluorescent dye ethidium bromide, while having no effect on cell membrane integrity. Alternatively, a corresponding peptide in which the TM4 binding motif is scrambled was inactive in this assay. In addition, when Escherichia coli cells expressing PAsmr were combined with sublethal concentrations of several biocides, growth was significantly inhibited when peptide was added, notably, by up to 95% with the disinfectant benzylalkonium chloride. These results demonstrate promise for an efflux pump inhibitor to address the increasing threat of antibiotic-resistant bacteria.