Nurse-led care for people with early rheumatoid arthritis: Interview study with thematic analysis.

AIMS: To develop an understanding of what comprises nurse-led care in early rheumatoid arthritis from the perspective of rheumatology nurse specialists in England. DESIGN: Qualitative study. METHODS: Semi-structured telephone interviews with rheumatology nurse specialists in England were conducted in Summer 2020. Interviews were audio-recorded, transcribed verbatim and analysed using reflexive thematic analysis. Reporting follows the appropriate elements of consolidated criteria for reporting qualitative research. RESULTS: Sixteen nurses were recruited and interviews lasted 30-60 min. Four themes with 14 subthemes were identified. A SPECIALIST SERVICE DELIVERED BY EXPERIENCED RHEUMATOLOGY NURSES: Specialist care is provided by experienced nurse specialists with a high degree of autonomy in the rheumatology multidisciplinary team context. ADDRESSING PATIENTS' COMPLEX CARE NEEDS: Care is evidence-based and aims to start treatment, keep in treatment, educate and support. Access to psychology expertise is needed. CARE WITH COMPASSION USING PERSON-CENTRED, HOLISTIC AND EMPATHETIC APPROACHES: Nurses create patient relationships and a positive therapeutic environment. Nurse-led telephone advice lines are essential for treatment adjustment, patient support and empowerment. CONTINUED EVALUATION AND DEVELOPMENT OF THE SERVICE: Consultations are reviewed, and patients are asked for feedback. The COVID-19 pandemic caused disruption, but changes streamlined procedures and improved documentation and communication. CONCLUSION: Nurse-led care in early rheumatoid arthritis is a specialist service delivered with compassion, addressing complex care needs and using person-centred approaches. This study identifies key aspects of care in early disease from the nurse perspective.

Systematic co-development and testing of a digital behaviour change intervention for osteoarthritis and physical activity: Theoretical mapping and acceptability study.

Objective: Osteoarthritis (OA) affects 8.75 million people in the UK. Physical activity (PA) is recommended as a core treatment, yet nearly half of people with OA are inactive. Accessible and user-friendly interventions are needed to motivate people with OA to be active. Digital behaviour change interventions (DBCIs) might help to support people with OA to self-manage their own levels of PA. The aim of this project was to co-develop and test a DBCI to motivate people with OA to be active. Methods: A mixed methods design was adopted to build the theoretical foundations, develop, and test a complex DBCI. Two patient research partners with lived experience of OA were recruited onto the project team to assist with intervention development, which was guided by the intervention mapping (IM) approach. Interviews and think-aloud sessions were then used to explore attitudes, values, and perceived effectiveness of the website. Results: The IM approach enabled the development of a prototype website to be illustrated in a clear and transparent way, showing a link between the practical materials adopted within the website and the theoretical constructs they were attempting to change. Potential users highlighted the importance of clear, easy-to-understand information, focusing on enjoyment and social connectedness. Conclusions: DBCI development should be based on theory, adequately described, and thoroughly tested with potential users to understand how they might choose to integrate digital interventions into everyday life.

Continuing the legacy of a military women's health research interest group.

The Military Women's Health Research Interest Group (MWHRIG) was established in 2010. The purpose of the MWHRIG is to support military clinicians and leaders in determining research priorities, and making evidence-based practice and policy decisions relevant to sex- and gender-appropriate healthcare. This article highlights the history of the MWHRIG, and current activities inclusive of research, mentorship, and collaboration. Future activities for the MWHRIG will focus on continued use of a theoretical framework for military women's health research, inclusivity of gender sexual diversity (GSD), and metrics for future success.

Meckel's Diverticulum - Clinical Presentation and Pitfalls in Diagnosis in the Pediatric Age Group in Singapore.

Purpose: The purpose of this study was to study the presentation of patients who underwent Meckel's diverticulectomy (MD) and utility of pertechnetate Meckel's scan in the diagnosis of MD. Methods: The clinical presentation of a retrospective cohort of patients who underwent MD from January 2007 to December 2019 was studied. The modes of presentation, treatment, and the diagnostic utility of pertechnetate Meckel's scans were evaluated. False-positive and false-negative scans were reviewed. The presence of gastric mucosa on histology of Meckel's was correlated with presentation as gastrointestinal bleeding and positive scan results. Results: Ninety-nine patients underwent MD. Thirty-five out of 263 (13.3%) Meckel's scans done were positive. There was a male preponderance (86.9%). The peak age of presentation was 0-4 years (rectal bleeding or intestinal obstruction). Only a third of the patients with Meckel's diverticulum Meckel's had a preoperative diagnosis of Meckel's. The sensitivity/specificity of Meckel's scan was higher in patients presenting with painless rectal bleeding. Seven patients were false positive (weak tracer uptake or ectopic uptake) and five were false negative. Two patients with false-negative Meckel's scan, having gastrointestinal bleeding had gastric mucosa on histology of Meckel's. Conclusion: Meckel's diverticulum has a male predominance. Meckel's scan has a high sensitivity in the children presenting with fresh painless rectal bleeding but is of limited use in the diagnosis of Meckel's diverticulum in other forms of presentations. False-positive scans can be anticipated in the presence of weak or ectopic uptake. False-negative scans can occur even in the presence of bleeding and in spite of the presence of gastric mucosa in the Meckel's diverticulum. Laparoscopy is a useful tool in diagnosis and treatment.

Anti-CRISPRdb v2.2: an online repository of anti-CRISPR proteins including information on inhibitory mechanisms, activities and neighbors of curated anti-CRISPR proteins.

We previously released the Anti-CRISPRdb database hosting anti-CRISPR proteins (Acrs) and associated information. Since then, the number of known Acr families, types, structures and inhibitory activities has accumulated over time, and Acr neighbors can be used as a candidate pool for screening Acrs in further studies. Therefore, we here updated the database to include the new available information. Our newly updated database shows several improvements: (i) it comprises more entries and families because it includes both Acrs reported in the most recent literatures and Acrs obtained via performing homologous alignment; (ii) the prediction of Acr neighbors is integrated into Anti-CRISPRdb v2.2, and users can identify novel Acrs from these candidates; and (iii) this version includes experimental information on the inhibitory strength and stage for Acr-Cas/Acr-CRISPR pairs, motivating the development of tools for predicting specific inhibitory abilities. Additionally, a parameter, the rank of codon usage bias (CUBRank), was proposed and provided in the new version, which showed a positive relationship with predicted result from AcRanker; hence, it can be used as an indicator for proteins to be Acrs. CUBRank can be used to estimate the possibility of genes occurring within genome island-a hotspot hosting potential genes encoding Acrs. Based on CUBRank and Anti-CRISPRdb, we also gave the first glimpse for the emergence of Acr genes (acrs). DATABASE URL: http://guolab.whu.edu.cn/anti-CRISPRdb.

Beliefs, motives and gains associated with physical activity in people with osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) affects approximately 8.75 million people in the United Kingdom. Physical activity is recommended as a core treatment, yet 44% of people with OA are inactive. Motivation and self-efficacy for exercise are considered to be key factors contributing to sustained engagement with physical activity. The aim of this study was to explore the beliefs, motives (what an individual aims to attain through participating in physical activity) and gains (what people feel they might get from participation) associated with physical activity engagement in a group of people with OA. DESIGN AND METHOD: This study adopted a cross-sectional survey research design, using two validated questionnaires: the Exercise Motives and Gains Inventory and the Exercise Self-Efficacy Scale. RESULTS: Data were gathered from 262 people with OA between August 2015 and January 2016. Those who were most active reported higher levels of both motivation and self-efficacy and were active for enjoyment, to avoid negative health, and for health and fitness reasons. A comparison of motives and gains revealed higher gain scores for social engagement and enjoyment, compared with associated motive scores. CONCLUSION: This study provides evidence of the central role that motives, gains and self-efficacy play in facilitating engagement with physical activity in this population. Future interventions should aim to foster increased self-efficacy for physical activity and promote autonomous forms of motivation by emphasising the importance of choosing activities which are enjoyable, as well as highlighting the value of social engagement.

Home-Initiated-Programme-to-Prepare-for-Operation: evaluating the effect of an animation video on peri-operative anxiety in children: A randomised controlled trial.

BACKGROUND: Hospital admissions and surgical operations commonly trigger anxiety in young children. Despite employing numerous support measures in our hospital, such as a pre-operative play room, the encouragement of parental companionship during induction of anaesthesia and distraction therapy, allaying the anxiety of our young surgical patients remains a challenge. OBJECTIVES: To evaluate the effectiveness of a Home-Initiated-Programme-to-Prepare-for-Operation (HIPPO) on emotional manifestation and anxiety in children undergoing surgery. DESIGN, SETTING AND PATIENTS: One hundred and thirty children were randomly assigned to either control or intervention group between February 2018 and April 2019 in a tertiary paediatric hospital in Singapore. INTERVENTION: In addition to our standard pre-operative workflow, the intervention group received an additional home preparation kit consisting of an animated video on preoperative preparation and age-specific preoperative preparation activity sheets. MAIN OUTCOME MEASURES: The primary outcome was the Children's Emotional Manifestation Scale score to evaluate behaviour and emotion in the children before and during induction of anaesthesia. Secondary outcomes evaluated anxiety levels in parents and children, the child's behaviour and degree of co-operation using the State-Trait Anxiety Inventory scores, State-Trait Anxiety Inventory Children scores, the Induction Compliance Checklist scores, the Visual Analogue Scale scores for anxiety and the feedback questionnaire. RESULTS: The difference between the Children's Emotional Manifestation Scale score in control and intervention groups was not statistically significant. A promising difference was however observed in one of the secondary outcomes where the state-State-Trait Anxiety Inventory Children scores of 7 to 10-year olds in the intervention group almost reached significance; P = 0.067. CONCLUSION: Despite being a child-friendly, easily accessible and affordable tool for patient education, HIPPO did not reduce anxiety experienced by children in the pre-operative waiting area or during induction of anaesthesia. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT04271553.

Developing Translational Vaccines against Heroin and Fentanyl through Investigation of Adjuvants and Stability.

The nearly insurmountable adversity that accompanies opioid use disorder (OUD) creates life-altering complications for opioid users. To worsen matters, existing small-molecule drugs continue to inadequately address OUD due to their engagement of the opioid receptor, which can leave the user to deal with side effects and financial hardships from their repeated use. An alternative therapeutic approach utilizes endogenously generated antibodies through active vaccination to reduce the effect of opioids without modulating the opioid receptor. Here, we explore different adjuvants and storage conditions to improve opioid vaccine efficacy and shelf life. Our results revealed that inulin-based formulations (Advax) containing a CpG oligodeoxynucleotide (ODN) acted as effective adjuvants when combined with a heroin conjugate: immunized mice showed excellent recovery from heroin-induced antinociception accompanied by high titer, high opioid affinity serum antibodies similar to the immunopotentiating properties of traditional alum-based adjuvants. Moreover, nonhuman primates vaccinated with a heroin/fentanyl combination vaccine demonstrated potent antibody responses against opioids when formulated with both inulin and alum adjuvants. Finally, storing a freeze-dried opioid vaccine formulation maintained efficacy for up 1 year at room temperature. The results from our studies represent an advance toward a clinically feasible opioid vaccine.

CEG 2.0: an updated database of clusters of essential genes including eukaryotic organisms.

Essential genes are key elements for organisms to maintain their living. Building databases that store essential genes in the form of homologous clusters, rather than storing them as a singleton, can provide more enlightening information such as the general essentiality of homologous genes in multiple organisms. In 2013, the first database to store prokaryotic essential genes in clusters, CEG (Clusters of Essential Genes), was constructed. Afterward, the amount of available data for essential genes increased by a factor >3 since the last revision. Herein, we updated CEG to version 2, including more prokaryotic essential genes (from 16 gene datasets to 29 gene datasets) and newly added eukaryotic essential genes (nine species), specifically the human essential genes of 12 cancer cell lines. For prokaryotes, information associated with drug targets, such as protein structure, ligand-protein interaction, virulence factor and matched drugs, is also provided. Finally, we provided the service of essential gene prediction for both prokaryotes and eukaryotes. We hope our updated database will benefit more researchers in drug targets and evolutionary genomics. Database URL: http://cefg.uestc.cn/ceg.

Salivary biomarker for acute appendicitis in children: a pilot study.

PURPOSE: Assays of salivary biomarkers for diagnosis are gaining popularity in pediatric diseases due to their non-invasive nature. Our pilot project aims to evaluate the utility of salivary leucine-rich-alpha-2-glycoprotein (LRG) in the diagnosis of pediatric acute appendicitis (AA). METHODS: We prospectively recruited 34 patients, aged between 4 and 16 years, admitted with acute abdominal pain suspicious of appendicitis. The patients' demography, clinical characteristics, laboratory investigations, imaging examination results, operative findings, and discharge diagnoses were recorded. We compared the diagnostic performance of the patients' total white counts, neutrophil percentages, C-reactive protein, and saliva LRG levels. Saliva samples were obtained using the SalivaBio Children's Swab and LRG levels were quantified using a commercially available LRG enzyme-linked immunosorbent assay (ELISA) kit. IRB approval was obtained. RESULTS: Seventeen patients had a confirmed diagnosis of appendicitis on histology. Another 17 were confirmed not to have appendicitis after a minimum of 24 h of hospitalization, with further verification via telephone interview 2 weeks later. The median levels of saliva LRG were elevated in patients with AA as compared to those without (P = 0.008). At a cutoff of LRG 0.33 ng/µg, we obtained a diagnostic specificity of 100% and sensitivity of 35.3%. CONCLUSION: Our proof-of-concept study demonstrated the diagnostic potential of saliva LRG for appendicitis in children. The distinct advantage of saliva LRG assays is that the procedure is simple, pain-free, and requires no specialized skill. Further study with a larger cohort is needed to verify our results.

Time course response of inflammatory markers in pediatric appendicitis.

PURPOSE: We aim to evaluate the diagnostic value and time course response of the triple inflammatory markers: white blood cell count (WBC), neutrophil percentage (Neu), and C-reactive protein (CRP) in pediatric acute appendicitis. METHODS: A retrospective review of clinical data pertaining to 1391 patients admitted with suspicion for pediatric appendicitis from 2012 to 2017 was conducted. Triple inflammatory markers were acquired upon admission. Appendicitis was confirmed histologically post-appendectomy. The diagnostic value and time course response of these markers was trended in relation to the duration of abdominal pain on admission. RESULTS: 718 patients had histologically confirmed appendicitis. WBC and Neu demonstrate high sensitivity for early appendicitis at 94.6% and 80.0% at Day 1, while CRP demonstrates highest sensitivity of 97.9% at Day 4. The triple markers had poor overall diagnostic value when interpreted individually, however, had a high combined sensitivity of 99.7% and negative predictive value of 98.7% regardless of duration of disease. Overall negative appendectomy rate was 6.7% (n = 52). Among 19 patients with triple markers negative who underwent appendectomy, 17 (89.5%) were histologically normal. CONCLUSIONS: The triple inflammatory markers have limited diagnostic value when interpreted individually, but are strong discriminators of pediatric appendicitis when combined. Their high sensitivity and negative predictive value could potentially help patients avoid unnecessary admissions or costly imaging studies, and reduce negative appendectomy rates. In addition, their objective nature confers an advantage over existing clinical scoring systems which comprise subjective elements.

Parental preferences in treatment of acute uncomplicated appendicitis comparing surgery to conservative management with antibiotics and their views on research participation.

Studies show that conservative management in acute uncomplicated appendicitis (AUA) is an alternative to surgery. This study aims to determine factors affecting parental preference in management of AUA and their decision for research participation. We conducted surveys on parents whose children were admitted with suspicion of appendicitis but later confirmed not to have appendicitis. Information on appendicectomy versus conservative treatment with antibiotics was provided using a fixed script and standard information leaflet. Questionnaires covered factors influencing decisions, opinions regarding research, treatment preference and demographic data. We excluded parents not fluent in English. Of 113 respondents, 71(62.8%) chose antibiotics, 39(34.5%) chose appendicectomy, and 3(2.7%) had no preference. Reasons given for choosing antibiotics were fear of surgical risks and preferring less invasive treatment. Those choosing appendicectomy expressed preference for definitive treatment and fear of recurrence. Majority were against randomisation (n = 89, 78.8%) and blinding (n = 90, 79.7%). Over half found difficulty involving their child in research (n = 65, 57.5%). Most thought that research is important (66.4%) and beneficial to others (59.3%). Parents who perceived their child as healthy found research riskier (p = 0.039). Educated parents were more likely to find research beneficial to others (p = 0.012) but less accepting of randomisation (p = 0.001).Conclusion: More parents appear to prefer conservative treatment for acute uncomplicated appendicitis. Researchers must consider parental concerns regarding randomisation and blinding.What is Known:• Conservative management of acute uncomplicated appendicitis in paediatric patients is safe and effective, sparing the child the need for an operation; however, neither conservative nor surgical management is proven to be superior.• Randomised controlled trials provide the highest level of evidence, but it is challenging to recruit paediatric patients as participants in such clinical trials.What is New:• More parents prefer conservative management of uncomplicated appendicitis over surgical management for their children due to fear of surgical risks and complications• Randomisation in trial design is significantly associated with a parent's decision to reject their child's participation in a clinical trial.

A pilot study comparing parent and adolescent online health information seeking behaviours in elective pediatric surgical situations.

PURPOSE: Little is known of how children seek health information. This study evaluates online health information (OHI) seeking behaviours in adolescents undergoing major elective surgical procedures and compares responses within parent-child dyads. METHODS: With institutional approval, we prospectively surveyed parents of children admitted to our institution for major elective operations between November 2017 and November 2018, using convenience sampling. Patients aged 12 years and above were also invited. Each respondent completed an anonymized modification of a previously published survey on Internet usage. Chi squared tests were used for categorical data, with significance at P value < 0.05. RESULTS: Ninety-one parents and 19 patients (median age 15 years, range 12-18) responded, with 13 parent-child pairs. Daily Internet access was reported by 84 (93%) parents and 18 (95%) children, but OHI was sought in 77% of parents and 74% of children. Six (32%) children could not name their admitting condition, compared to 10 (11%) parents. Nine (50%) children consulted family and friends for information compared to 27 (30%) parents. Parents were more likely to access hospital websites (n = 15, 44%) compared to no children (p = 0.01), while most children (n = 7, 70%) accessed non-health websites (e.g. Wikipedia). In the 13 parent-child pairs, only one parent accurately assessed what their child understood of their condition. Most patients (63.6%) did not understand the aspects of their condition that their parents deemed important. CONCLUSIONS: This study highlights the differences in parental and child behaviours. Children are equally important to include when counselling. Surgeons can guide both parties to reliable Internet sources for health information.

Sensory Function and Pain Experience in Arthritis, Complex Regional Pain Syndrome, Fibromyalgia Syndrome, and Pain-Free Volunteers: A Cross-Sectional Study.

OBJECTIVES: This study aimed to identify relationships between sensory function and pain in 3 common pain conditions (arthritis, Complex Regional Pain Syndrome [CRPS] and fibromyalgia syndrome [FMS]) and pain-free participants. Sensory abnormalities are known to be concomitant with some types of chronic pain but comparison across pain conditions using existing research is difficult due to methodological differences. Pragmatic Quantitative Sensory Testing (QST) methods were used. MATERIALS AND METHODS: Hot and cold sensitivity, light touch threshold (LTT), two-point discrimination and pain threshold were assessed in 143 participants (n=37 pain-free, n=34 arthritis, n=36 CRPS, n=36 FMS). Outcomes were assessed in the index ("affected" or right) and contralateral arm. Participants also completed the Brief Pain Inventory and the McGill Pain Questionnaire. RESULTS: There were statistically significant differences between groups for all QST outcomes except two-point discrimination. Relative to pain-free participants, FMS displayed heat hyperesthesia in both arms and cold hyperesthesia in the contralateral arm. CRPS demonstrated no changes in thermal sensitivity. Both CRPS and FMS exhibited bilateral pressure hyperalgesia. LTT hypoesthesia was observed bilaterally for CRPS but only in the contralateral arm for FMS. CRPS and FMS had pressure hyperalgesia in the index arm relative to arthritis patients. There were no differences between arthritis and pain-free participants for any QST outcome. In CRPS, there were significant correlations between LTT and pain outcomes bilaterally. DISCUSSION: People with FMS and CRPS demonstrate extensive sensory dysfunction. Arthritis patients had sensory profiles closer to pain-free participants. LTT may provide a clinically relevant and accessible assessment for CRPS.

Vaccine blunts fentanyl potency in male rhesus monkeys.

One proposed factor contributing to the increased frequency of opioid overdose deaths is the emergence of novel synthetic opioids, including illicit fentanyl and fentanyl analogues. A treatment strategy currently under development to address the ongoing opioid crisis is immunopharmacotherapies or opioid-targeted vaccines. The present study determined the effectiveness and selectivity of a fentanyl-tetanus toxoid conjugate vaccine to alter the behavioral effects of fentanyl and a structurally dissimilar mu-opioid agonist oxycodone in male rhesus monkeys (n = 3-4). Fentanyl and oxycodone produced dose-dependent suppression of behavior in an assay of schedule-controlled responding and antinociception in an assay of thermal nociception (50 °C). Acute naltrexone (0.032 mg/kg) produced an approximate 10-fold potency shift for fentanyl to decrease operant responding. The fentanyl vaccine was administered at weeks 0, 2, 4, 9, 19, and 44 and fentanyl or oxycodone potencies in both behavioral assays were redetermined over the course of 49 weeks. The vaccine significantly and selectively shifted fentanyl potency at least 10-fold in both assays at several time points over the entire experimental period. Mid-point titer levels correlated with fentanyl antinociceptive potency shifts. Antibody affinity for fentanyl as measured by a competitive binding assay improved over time to approximately 3-4 nM. The fentanyl vaccine also increased fentanyl plasma levels approximately 6-fold consistent with the hypothesis that the vaccine sequesters fentanyl in the blood. Overall, these results support the continued development and evaluation of this fentanyl vaccine in humans to address the ongoing opioid crisis.

Heroin vaccine: Using titer, affinity, and antinociception as metrics when examining sex and strain differences.

Anti-drug vaccines have potential as new interventions against substance use disorder (SUD). However, given the challenges seen with inter-individual variability in SUD vaccine trials to date, new interventions should ensure a robust immune response and safety profile among a diverse population. This requires accounting for sex and heritable genetic differences in response to both abused substances as well as the vaccination itself. To test response variability to our heroin-tetanus toxoid (Her-TT) immunoconjugate vaccine, we vaccinated male and female mice from several mouse strains including Swiss Webster (SW), BALB/c, and Jackson diversity mice (J:DO). Previous studies with vaccinated male SW mice demonstrated a rare hypersensitivity resulting in mice rapidly expiring with exposure to a low dose of heroin. Our results indicate that this response is limited to only male SW mice, and not to any other strain or female SW mice. Our data suggest that this hypersensitivity is not the result of an overactive cytokine or IgE response. Vaccination was similarly effective among the sexes for each strain and against repeated heroin challenge. Inbred BALB/c and J:DO mice were found to have the best vaccine response against heroin in antinociception behavioral assay. These results highlight the importance of incorporating both male and female subjects, along with different strains to mimic diverse human populations, as new SUD vaccines are being tested.

Monoclonal Antibodies for Combating Synthetic Opioid Intoxication.

Opioid abuse in the United States has been declared a national crisis and is exacerbated by an inexpensive, readily available, and illicit supply of synthetic opioids. Specifically, fentanyl and related analogues such as carfentanil pose a significant danger to opioid users due to their high potency and rapid acting depression of respiration. In recent years these synthetic opioids have become the number one cause of drug-related deaths. In our research efforts to combat the public health threat posed by synthetic opioids, we have developed monoclonal antibodies (mAbs) against the fentanyl class of drugs. The mAbs were generated in hybridomas derived from mice vaccinated with a fentanyl conjugate vaccine. Guided by a surface plasmon resonance (SPR) binding assay, we selected six hybridomas that produced mAbs with 10-11 M binding affinity for fentanyl, yet broad cross-reactivity with related fentanyl analogues. In mouse antinociception models, our lead mAb (6A4) could blunt the effects of both fentanyl and carfentanil in a dose-responsive manner. Additionally, mice pretreated with 6A4 displayed enhanced survival when subjected to fentanyl above LD50 doses. Pharmacokinetic analysis revealed that the antibody sequesters large amounts of these drugs in the blood, thus reducing drug biodistribution to the brain and other tissue. Lastly, the 6A4 mAb could effectively reverse fentanyl/carfentanil-induced antinociception comparable to the opioid antagonist naloxone, the standard of care drug for treating opioid overdose. While naloxone is known for its short half-life, we found the half-life of 6A4 to be approximately 6 days in mice, thus monoclonal antibodies could theoretically be useful in preventing renarcotization events in which opioid intoxication recurs following quick metabolism of naloxone. Our results as a whole demonstrate that monoclonal antibodies could be a desirable treatment modality for synthetic opioid overdose and possibly opioid use disorder.

A chemically contiguous hapten approach for a heroin-fentanyl vaccine.

Background: Increased death due to the opioid epidemic in the United States has necessitated the development of new strategies to treat addiction. Monoclonal antibodies and antidrug vaccines provide a tool that both aids addiction management and reduces the potential for overdose. Dual drug vaccines formulated by successive conjugation or by mixture have certain drawbacks. The current study examines an approach for combatting the dangers of fentanyl-laced heroin, by using a hapten with one epitope that has domains for both fentanyl and heroin. Results: We evaluated a series of nine vaccines developed from chemically contiguous haptens composed of both heroin- and fentanyl-like domains. Analysis of the results obtained by SPR and ELISA revealed trends in antibody affinity and titers for heroin and fentanyl based on epitope size and linker location. In antinociception studies, the best performing vaccines offered comparable protection against heroin as our benchmark heroin vaccine, but exhibited attenuated protection against fentanyl compared to our fentanyl vaccine. Conclusion: After thorough investigation of this strategy, we have identified key considerations for the development of a chemically contiguous heroin-fentanyl vaccine. Importantly, this is the first report of such a strategy in the opioid-drug-vaccine field.

Conjugate vaccine produces long-lasting attenuation of fentanyl vs. food choice and blocks expression of opioid withdrawal-induced increases in fentanyl choice in rats.

The current opioid crisis remains a significant public health issue and there is a critical need for biomedical research to develop effective and easily deployable candidate treatments. One emerging treatment strategy for opioid use disorder includes immunopharmacotherapies or opioid-targeted vaccines. The present study determined the effectiveness of a fentanyl-tetanus toxoid conjugate vaccine to alter fentanyl self-administration using a fentanyl-vs.-food choice procedure in male and female rats under three experimental conditions. For comparison, continuous 7-day naltrexone (0.01-0.1 mg/kg/h) and 7-day clonidine (3.2-10 µg/kg/h) treatment effects were also determined on fentanyl-vs.-food choice. Male and female rats responded for concurrently available 18% diluted Ensure® (liquid food) and fentanyl (0-10 µg/kg/infusion) infusions during daily sessions. Under baseline and saline treatment conditions, fentanyl maintained a dose-dependent increase in fentanyl-vs.-food choice. First, fentanyl vaccine administration significantly blunted fentanyl reinforcement and increased food reinforcement for 15 weeks in non-opioid dependent rats. Second, surmountability experiments by increasing the unit fentanyl dose available during the self-administration session 10-fold empirically determined that the fentanyl vaccine produced an approximate 22-fold potency shift in fentanyl-vs.-food choice that was as effective as the clinically approved treatment naltrexone. Clonidine treatment significantly increased fentanyl-vs.-food choice. Lastly, fentanyl vaccine administration prevented the expression of withdrawal-associated increases in fentanyl-vs.-food choice following introduction of extended 12 h fentanyl access sessions. Overall, these results support the potential and further consideration of immunopharmacotherapies as candidate treatments to address the current opioid crisis.