Readiness of primary care centres for a community-based intervention to prevent and control noncommunicable diseases in the Caribbean: A participatory, mixed-methods study.

INTRODUCTION: Epidemiological transition to NCDs is a challenge for fragile health systems in the Caribbean. The Congregations Taking Action against NCDs (CONTACT) Study intervention proposes that trained health advocates (HAs) from places of worship (PoWs), supervised by nurses at nearby primary healthcare centres (PHCs), could facilitate access to primary care among vulnerable communities. Drawing on participatory and systems thinking, we explored the capacity of local PHCs in three Caribbean countries to support this intervention. METHODS: Communities in Jamaica (rural, urban), Guyana (rural) and Dominica (Indigenous Kalinago Territory) were selected for CONTACT because of their differing socio-economic, cultural, religious and health system contexts. Through mixed-method concept mapping, we co-developed a list of perceived actionable priorities (possible intervention points ranked highly for feasibility and importance) with 48 policy actors, healthcare practitioners and civic society representatives. Guided in part by the concept mapping findings, we assessed the readiness of 12 purposefully selected PHCs for the intervention, using a staff questionnaire and an observation checklist to identify enablers and constrainers. RESULTS: Concept mapping illustrated stakeholder optimism for the intervention, but revealed perceptions of inadequate primary healthcare service capacity, resources and staff training to support implementation. Readiness assessments of PHCs identified potential enablers and constrainers that were consistent with concept mapping results. Staff support was evident. Constraints included under-staffing, which could hinder supervision of HAs; and inadequate essential NCD medicines, training in NCDs and financial and policy support for embedding community interventions. Despite a history of socio-political disadvantage, the most enabling context was found in the Kalinago Territory, where ongoing community engagement activities could support joint development of programmes between churches and PHCs. CONCLUSION: Multi-sectoral stakeholder consultation and direct PHC assessments revealed viability of the proposed POW-PHC partnership for NCD prevention and control. However, structural and policy support will be key for implementing change.

Transforming dementia research into policy change: A case study of the multi-country STRiDE project.

STRiDE was an ambitious four-year project in seven countries aiming to build capacity around generating and using research to support the development of policies to improve quality of life of people with dementia and their carers. The project's innovative approach combined rigorous academic research and hands-on civil society advocacy. This paper explores the project's unique strategy for policy change and compiles case-studies from several of the STRiDE countries. Finally, we share lessons learned and next steps to keep momentum for policy change going in each of these countries - and beyond.

The barriers and facilitators to physical activity in people with a musculoskeletal condition: A rapid review of reviews using the COM-B model to support intervention development.

Objectives: The objective of this review of reviews was to identify the potentially modifiable barriers and facilitators to physical activity in people with a musculoskeletal condition to influence intervention development. Study design: A rapid review of reviews. Methods: The Cochrane library and PubMed Central were searched for reviews using pre-defined search terms and relevant synonyms for "physical activity", "barriers" or "facilitators", and "musculoskeletal condition". The identified reviews were screened for inclusion by the principal investigator in line with recognised streamlining approaches for a rapid review. Only review papers investigating the barriers and facilitators to physical activity in adults with a musculoskeletal condition were included. A team of seven assessed the included reviews for identification of the barriers and facilitators to physical activity coded using the COM-B model of behaviour. Results: 503 reviews were identified with 12 included for analysis across a mix of conditions and designs (n = 2: qualitative; n = 6: quantitative; n = 4 mixed). A multitude of interrelated factors were identified across the COM-B components. The most prevalent factors included disease symptoms and physical function (physical capability), knowledge of the specific benefits of physical activity and knowing what to do (psychological capability), the accessibility of facilities and individualised programming (physical opportunity), tailored advice from healthcare professionals and peer support (social opportunity), beliefs about the benefits or harms of being active (reflective motivation) and having the self-efficacy to be active and experiencing positive emotions (automatic motivation). Conclusions: This review of reviews identified the complex nature of physical activity in people living with a musculoskeletal condition. The identified barriers and facilitators should be considered by intervention designers when developing behaviour change interventions for this population group.

Beyond the project: Building a strategic theory of change to address dementia care, treatment and support gaps across seven middle-income countries.

Evidence from middle-income countries indicates high and increasing prevalence of dementia and need for services. However, there has been little investment in care, treatment or support for people living with dementia and their carers. The Strengthening Responses to Dementia in Developing Countries (STRiDE) project aims to build both research capacity and evidence on dementia care and services in Brazil, Indonesia, India, Jamaica, Kenya, Mexico and South Africa. This article presents the Theory of Change (ToC) approach we used to co-design our research project and to develop a strategic direction for dementia care, treatment and support, with stakeholders. ToC makes explicit the process underlying how a programme will achieve its impact. We developed ToCs in each country and across the STRiDE project with researchers, practitioners, people living with dementia, carers and policymakers at different levels of government. This involved (1) an initial ToC workshop with all project partners (43 participants); (2) ToC workshops in each STRiDE country (22-49 participants in each); (3) comparison between country-specific and overall project ToCs; (4) review of ToCs in light of WHO dementia guidelines and action plan and (5) a final review. Our experiences suggest ToC is an effective way to generate a shared vision for dementia care, treatment and support among diverse stakeholders. However, the project contribution should be clearly delineated and use additional strategies to ensure appropriate participation from people living with dementia and their carers in the ToC process.

ETX2514 is a broad-spectrum ß-lactamase inhibitor for the treatment of drug-resistant Gram-negative bacteria including Acinetobacter baumannii.

Multidrug-resistant (MDR) bacterial infections are a serious threat to public health. Among the most alarming resistance trends is the rapid rise in the number and diversity of ß-lactamases, enzymes that inactivate ß-lactams, a class of antibiotics that has been a therapeutic mainstay for decades. Although several new ß-lactamase inhibitors have been approved or are in clinical trials, their spectra of activity do not address MDR pathogens such as Acinetobacter baumannii. This report describes the rational design and characterization of expanded-spectrum serine ß-lactamase inhibitors that potently inhibit clinically relevant class A, C and D ß-lactamases and penicillin-binding proteins, resulting in intrinsic antibacterial activity against Enterobacteriaceae and restoration of ß-lactam activity in a broad range of MDR Gram-negative pathogens. One of the most promising combinations is sulbactam-ETX2514, whose potent antibacterial activity, in vivo efficacy against MDR A. baumannii infections and promising preclinical safety demonstrate its potential to address this significant unmet medical need.

"Christ offered salvation, and not an easy life": How do port chaplains make sense of providing welfare for seafarers? An idiographic, phenomenological approach analysis.

BACKGROUND: The shipping industry has historically leaned towards a biomedical model of health when assessing, treating and caring for seafarers. In recent years there has been more concern for the mental health of seafarers in both the academic literature and the commercial world, however, the psychological and emotional well-being of seafarers still largely falls on the shoulders of the port chaplains. The aim of the study was to explore how port chaplains make sense of providing welfare for seafarers by taking an idiographic, phenomenological approach (IPA). MATERIALS AND METHODS: Six male participants working as chaplains in United Kingdom ports took part in recorded face-to-face, semi-structured interviews covering three areas of questioning: role, identity and coping. Interviews were transcribed verbatim, and data analysed using interpretative phenomenological analysis. RESULTS: Three super-ordinate themes were identified from participants accounts; "We walk a very strange and middle path", "Exploited" and "Patching up". Rich data emerged in relation to the personal impact chaplains felt they made, which was facilitated by the historical role of the Church; this led to the second super-ordinate theme of how chaplains felt towards seafarers. Lastly, the analysis demonstrates how chaplains adapt to the limitations forced upon them to provide welfare, and a degree of acceptance at the injustice. CONCLUSIONS: Results were discussed in reference to theoretical models, including self-efficacy, empathic responding and the transactional model of stress and coping. Chaplains in ports perform their role autonomously with no input from healthcare professionals. Recommendations are made for a biopsychosocial model of health involving primary care, benefiting the health and well-being of seafarers and providing support and guidance for port chaplains at the frontline of welfare for seafarers.

Inhibition of Neisseria gonorrhoeae Type II Topoisomerases by the Novel Spiropyrimidinetrione AZD0914.

We characterized the inhibition of Neisseria gonorrhoeae type II topoisomerases gyrase and topoisomerase IV by AZD0914 (AZD0914 will be henceforth known as ETX0914 (Entasis Therapeutics)), a novel spiropyrimidinetrione antibacterial compound that is currently in clinical trials for treatment of drug-resistant gonorrhea. AZD0914 has potent bactericidal activity against N. gonorrhoeae, including multidrug-resistant strains and key Gram-positive, fastidious Gram-negative, atypical, and anaerobic bacterial species (Huband, M. D., Bradford, P. A., Otterson, L. G., Basrab, G. S., Giacobe, R. A., Patey, S. A., Kutschke, A. C., Johnstone, M. R., Potter, M. E., Miller, P. F., and Mueller, J. P. (2014) In Vitro Antibacterial Activity of AZD0914: A New Spiropyrimidinetrione DNA Gyrase/Topoisomerase Inhibitor with Potent Activity against Gram-positive, Fastidious Gram-negative, and Atypical Bacteria. Antimicrob. Agents Chemother. 59, 467-474). AZD0914 inhibited DNA biosynthesis preferentially to other macromolecules in Escherichia coli and induced the SOS response to DNA damage in E. coli. AZD0914 stabilized the enzyme-DNA cleaved complex for N. gonorrhoeae gyrase and topoisomerase IV. The potency of AZD0914 for inhibition of supercoiling and the stabilization of cleaved complex by N. gonorrhoeae gyrase increased in a fluoroquinolone-resistant mutant enzyme. When a mutation, conferring mild resistance to AZD0914, was present in the fluoroquinolone-resistant mutant, the potency of ciprofloxacin for inhibition of supercoiling and stabilization of cleaved complex was increased greater than 20-fold. In contrast to ciprofloxacin, religation of the cleaved DNA did not occur in the presence of AZD0914 upon removal of magnesium from the DNA-gyrase-inhibitor complex. AZD0914 had relatively low potency for inhibition of human type II topoisomerases α and ß.

Selection and molecular characterization of ceftazidime/avibactam-resistant mutants in Pseudomonas aeruginosa strains containing derepressed AmpC.

OBJECTIVES: Pseudomonas aeruginosa is an important nosocomial pathogen that can cause a wide range of infections resulting in significant morbidity and mortality. Avibactam, a novel non-ß-lactam ß-lactamase inhibitor, is being developed in combination with ceftazidime and has the potential to be a valuable addition to the treatment options for the infectious diseases practitioner. We compared the frequency of resistance development to ceftazidime/avibactam in three P. aeruginosa strains that carried derepressed ampC alleles. METHODS: The strains were incubated in the presence of increasing concentrations of ceftazidime with a fixed concentration (4 mg/L) of avibactam to calculate the frequency of spontaneous resistance. The mutants were characterized by WGS to identify the underlying mechanism of resistance. A representative mutant protein was characterized biochemically. RESULTS: The resistance frequency was very low in all strains. The resistant variants isolated exhibited ceftazidime/avibactam MIC values that ranged from 64 to 256 mg/L. All of the mutants exhibited changes in the chromosomal ampC gene, the majority of which were deletions of various sizes in the Ω-loop region of AmpC. The mutant enzyme that carried the smallest Ω-loop deletion, which formed a part of the avibactam-binding pocket, was characterized biochemically and found to be less effectively inhibited by avibactam as well as exhibiting increased hydrolysis of ceftazidime. CONCLUSIONS: The development of high-level resistance to ceftazidime/avibactam appears to occur at low frequency, but structural modifications in AmpC can occur that impact the ability of avibactam to inhibit the enzyme and thereby protect ceftazidime from hydrolysis.

Alkylidene Oxapenem ß-Lactamase Inhibitors Revisited: Potent Broad Spectrum Activity but New Stability Challenges.

We present a comprehensive study of C6-alkylidene containing oxapenems. We show that this class of ß-lactamase inhibitors possesses an unprecedented spectrum with activity against class A, C, and D enzymes. Surprisingly, this class of compounds displayed significant photolytic instability in addition to the known hydrolytic instability. Quantum mechanical calculations were used to develop models to predict the stability of new analogues.

Kinetics of avibactam inhibition against Class A, C, and D ß-lactamases.

Avibactam is a non-ß-lactam ß-lactamase inhibitor with a spectrum of activity that includes ß-lactamase enzymes of classes A, C, and selected D examples. In this work acylation and deacylation rates were measured against the clinically important enzymes CTX-M-15, KPC-2, Enterobacter cloacae AmpC, Pseudomonas aeruginosa AmpC, OXA-10, and OXA-48. The efficiency of acylation (k2/Ki) varied across the enzyme spectrum, from 1.1 × 10(1) m(-1)s(-1) for OXA-10 to 1.0 × 10(5) for CTX-M-15. Inhibition of OXA-10 was shown to follow the covalent reversible mechanism, and the acylated OXA-10 displayed the longest residence time for deacylation, with a half-life of greater than 5 days. Across multiple enzymes, acyl enzyme stability was assessed by mass spectrometry. These inhibited enzyme forms were stable to rearrangement or hydrolysis, with the exception of KPC-2. KPC-2 displayed a slow hydrolytic route that involved fragmentation of the acyl-avibactam complex. The identity of released degradation products was investigated, and a possible mechanism for the slow deacylation from KPC-2 is proposed.

Evaluation of a tuberculosis education video among immigrants and refugees at an adult education center: a community-based participatory approach.

Tuberculosis disproportionately affects immigrants and refugees to the United States. Upon arrival to the United States, many of these individuals attend adult education centers, but little is known about how to deliver tuberculosis health information at these venues. Therefore, the authors used a participatory approach to design and evaluate a tuberculosis education video in this setting. The authors used focus group data to inform the content of the video that was produced and delivered by adult learners and their teachers. The video was evaluated by learners for acceptability through 3 items with a 3-point Likert scale. Knowledge (4 items) and self-efficacy (2 items) about tuberculosis were evaluated before and after viewing the video. A total of 159 learners (94%) rated the video as highly acceptable. Knowledge about tuberculosis improved after viewing the video (56% correct vs. 82% correct; p <.001), as did tuberculosis-related self-efficacy (77% vs. 90%; p <.001). Adult education centers that serve large immigrant and refugee populations may be excellent venues for health education, and a video may be an effective tool to educate these populations. Furthermore, a participatory approach in designing health education materials may enhance the efficacy of these tools.

Isolation of Equine rhinitis A virus from a horse semen sample.

Semen from an apparently healthy 4-year-old American Quarter Horse was submitted to the National Veterinary Services Laboratories for Equine arteritis virus isolation. Visual inspection of the semen sample upon arrival noted it was unusually yellow in color. The semen sample was inoculated onto cell monolayers, and cytopathic effect was observed 5 days postinoculation. The resultant isolate tested negative for Equine arteritis virus, and was subsequently identified as Equine rhinitis A virus. Equine rhinitis A virus has been isolated from horse urine, but has not been described in stallion semen. The present study documents the isolation of Equine rhinitis A virus from stallion semen that was likely contaminated with urine at the time of collection.

Physical activity and nutrition among immigrant and refugee women: a community-based participatory research approach.

BACKGROUND: Immigrant and refugee populations arrive to the U.S. healthier than the general population, but the longer they reside, the more they approximate the cardiovascular risk profiles of the country. Among women, these declines are partly mediated by less physical activity and lower dietary quality upon immigration. Given the complex forces that influence these behaviors, a community-based participatory research (CBPR) approach is appropriate. Therefore, a socioculturally responsive physical activity and nutrition program was created with and for immigrant and refugee women in Rochester, Minnesota, through a CBPR approach. METHODS: Focus groups informed program content and revealed principles for designing the sessions. A 6-week program with two, 90-minute classes per week was conducted among 45 women (Hispanic, Somali, Cambodian, and non-immigrant African American). Average attendance was 22.5 women per class; 34 women completed the evaluation. RESULTS: Evaluation revealed high acceptability (average overall score of 4.85 out of 5 on the Physical Activity Class Satisfaction Questionnaire). After the intervention, participants were more likely to exercise regularly (p ≤ .001). They reported higher health-related quality of life (p ≤ .001) and self-efficacy for diet (p = .36) and exercise (p = .10). Likewise, there were trends for weight loss (87 vs 83.4 kg; p = .65), decreased waist circumference (99.6 vs 95.5 cm; p = .35), and lower blood pressure (125/80 vs 122/76 mm/Hg; p = .27). CONCLUSION: A CBPR approach to design and implement a socioculturally responsive fitness program was highly acceptable to immigrant and refugee women and demonstrated promising outcomes. Further testing of physical activity and nutrition interventions that arise organically from target communities are needed.