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Background: Patient information may assist in promoting shared decision-making, however it is imperative that the information presented is comprehensible and acceptable to the target audience. Objective: This study sought to explore the acceptability and comprehensibility of the ‘Medicines in Scotland: What’s the right treatment for you?’ factsheet to the general public. Methods: Qualitative semi-structured telephone interviews were conducted with members of the public. An interview schedule was developed to explore the acceptability and comprehensibility of the factsheet. Participants were recruited by a researcher who distributed information packs to attendees (n=70) of four community pharmacies. Interviews, (12-24 minutes duration), were audio recorded, transcribed verbatim and analysed using a framework approach. Results: Nineteen participants returned a consent form (27.1%), twelve were interviewed. Six themes were identified: formatting of the factsheet and interpretation; prior health knowledge and the factsheet; information contained in the factsheet; impact of the factsheet on behaviour; uses for the factsheet; and revisions to the factsheet. Conclusions: The factsheet was generally perceived as helpful and comprehensive. It was highlighted that reading the leaflet may generate new knowledge and may have a positive impact on behaviour.

Abstract Background The ability to differentiate a bioterrorist attack or an accidental release of a research pathogen from a naturally occurring pandemic or disease event is crucial to the safety and security of this nation by enabling an appropriate and rapid response. It is critical in samples from an infected patient, the environment, or a laboratory to quickly and accurately identify the precise pathogen including natural or engineered variants and to classify new pathogens in relation to those that are known. Current approaches for pathogen detection rely on prior genomic sequence information. Given the enormous spectrum of genetic possibilities, a field deployable, robust technology, such as a universal (any species) microarray has near-term potential to address these needs. Results A new and comprehensive sequence-independent array (Universal Bio-Signature Detection Array) was designed with approximately 373,000 probes. The main feature of this array is that the probes are computationally derived and sequence independent. There is one probe for each possible 9-mer sequence, thus 49 (262,144) probes. Each genome hybridized on this array has a unique pattern of signal intensities corresponding to each of these probes. These signal intensities were used to generate an un-biased cluster analysis of signal intensity hybridization patterns that can easily distinguish species into accepted and known phylogenomic relationships. Within limits, the array is highly sensitive and is able to detect synthetically mixed pathogens. Examples of unique hybridization signal intensity patterns are presented for different Brucella species as well as relevant host species and other pathogens. These results demonstrate the utility of the UBDA array as a diagnostic tool in pathogen forensics. Conclusions This pathogen detection system is fast, accurate and can be applied to any species. Hybridization patterns are unique to a specific genome and these can be used to decipher the identity of a mixed pathogen sample and can separate hosts and pathogens into their respective phylogenomic relationships. This technology can also differentiate between different species and classify genomes into their known clades. The development of this technology will result in the creation of an integrated biomarker-specific bio-signature, multiple select agent specific detection system.

To explore the effects of climate change on malaria and 20 neglected tropical diseases (NTDs), and potential effect amelioration through mitigation and adaptation, we searched for papers published from January 2010 to October 2023. We descriptively synthesised extracted data. We analysed numbers of papers meeting our inclusion criteria by country and national disease burden, healthcare access and quality index (HAQI), as well as by climate vulnerability score. From 42 693 retrieved records, 1543 full-text papers were assessed. Of 511 papers meeting the inclusion criteria, 185 studied malaria, 181 dengue and chikungunya and 53 leishmaniasis; other NTDs were relatively understudied. Mitigation was considered in 174 papers (34%) and adaption strategies in 24 (5%). Amplitude and direction of effects of climate change on malaria and NTDs are likely to vary by disease and location, be non-linear and evolve over time. Available analyses do not allow confident prediction of the overall global impact of climate change on these diseases. For dengue and chikungunya and the group of non-vector-borne NTDs, the literature privileged consideration of current low-burden countries with a high HAQI. No leishmaniasis papers considered outcomes in East Africa. Comprehensive, collaborative and standardised modelling efforts are needed to better understand how climate change will directly and indirectly affect malaria and NTDs., (© World Health Organization, 2024. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.)

Aberrant activity in caudal subcallosal anterior cingulate cortex (scACC) is implicated in depression and anxiety symptomatology, with its normalisation a putative biomarker of successful treatment response. The function of scACC in emotion processing and mental health is not fully understood despite its known influence on stress-mediated processes through its rich expression of mineralocorticoid and glucocorticoid receptors. Here we examine the causal interaction between area 25 within scACC (scACC-25) and the stress hormone, cortisol, in the context of anhedonia and anxiety-like behaviour. In addition, the overall role of scACC-25 in hedonic capacity and motivation is investigated under transient pharmacological inactivation and overactivation. The results suggest that a local increase of cortisol in scACC-25 shows a rapid induction of anticipatory anhedonia and increased responsiveness to uncertain threat. Separate inactivation and overactivation of scACC-25 increased and decreased motivation and hedonic capacity, respectively, likely through different underlying mechanisms. Together, these data show that area scACC-25 has a causal role in consummatory and motivational behaviour and produces rapid responses to the stress hormone cortisol, that mediates anhedonia and anxiety-like behaviour., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Antimicrobial resistance (AMR) is included in the ten most urgent global public health threats. Global evidence suggests that antibiotics were over prescribed during the early waves of the COVID-19 pandemic, particularly in low- and middle-income countries. Inappropriate use of antibiotics drives the emergence and spread of antibiotic resistance. This study aimed to examine the impact of COVID-19 on Ni-Vanuatu health worker knowledge, beliefs, and practices (KBP) regarding antibiotic prescribing and awareness of antibacterial AMR. A mixed methods study was conducted using questionnaires and in-depth interviews in 2018 and 2022. A total of 49 respondents completed both baseline (2018) and follow-up (2022) questionnaires. Knowledge scores about prescribing improved between surveys, although health workers were less confident about some prescribing activities. Respondents identified barriers to optimal hand hygiene performance. More than three-quarters of respondents reported that COVID-19 influenced their prescribing practice and heightened their awareness of ABR: "more careful", "more aware", "stricter", and "need more community awareness". Recommendations include providing ongoing continuing professional development to improve knowledge, enhance skills, and maintain prescribing competency; formalising antibiotic stewardship and infection, prevention, and control (IPC) programmes to optimise prescribing and IPC practices; and raising community awareness about ABR to support more effective use of medications.

Objective: Prior studies on the gut microbiome in Parkinson's disease (PD) have yielded conflicting results, and few studies have focused on prodromal (premotor) PD or used shotgun metagenomic profiling to assess microbial functional potential. We conducted a nested case-control study within 2 large epidemiological cohorts to examine the role of the gut microbiome in PD., Methods: We profiled the fecal metagenomes of 420 participants in the Nurses' Health Study and the Health Professionals Follow-up Study with recent onset PD (N = 75), with features of prodromal PD (N = 101), controls with constipation (N = 113), and healthy controls (N = 131) to identify microbial taxonomic and functional features associated with PD and features suggestive of prodromal PD. Omnibus and feature-wise analyses identified bacterial species and pathways associated with prodromal and recently onset PD., Results: We observed depletion of several strict anaerobes associated with reduced inflammation among participants with PD or features of prodromal PD. A microbiome-based classifier had moderate accuracy (area under the curve [AUC] = 0.76 for species and 0.74 for pathways) to discriminate between recently onset PD cases and controls. These taxonomic shifts corresponded with functional shifts indicative of carbohydrate source preference. Similar, but less marked, changes were observed in participants with features of prodromal PD, in both microbial features and functions., Interpretation: PD and features of prodromal PD were associated with similar changes in the gut microbiome. These findings suggest that changes in the microbiome could represent novel biomarkers for the earliest phases of PD. ANN NEUROL 2023;94:486-501., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure., Methods: We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites., Results: Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease., Conclusions: Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention., (© 2023. The Author(s).)

Objectives: The aim of this study was to explore the public's current awareness of the safe use of medicines in general, and over-the-counter (OTC) analgesics (painkillers) in particular, as well as their information-seeking and advice-seeking, medicine use and disposal., Setting: General population, Scotland., Participants: Adults (aged >16 years) living in Scotland., Interventions: A cross-sectional survey was undertaken in collaboration with Ipsos MORI (a market research company). The content was informed by a multi-stakeholder prioritisation event and supplemented with information from earlier studies., Results: The survey was completed in March 2020 by 1000 respondents, most of whom had used a pharmacy in the previous 12 months to obtain a medicine. Of the 1000 respondents, 39% (n=389) were 55 years and over; 52% (n=517) were women; and 58% were degree-educated.On receipt of a new prescription, up to 29.8% (95% CI 27.0% to 32.7%) of respondents proactively sought specific information or advice from the pharmacist. Few (5.2% (95% CI 4.0% to 6.8%) respondents 'always' discussed their new prescription medicine with pharmacy staff and 28.9% (95% CI 26.2% to 31.8%) reported 'never' engaging in this behaviour. Respondents aged >35 years were less likely to engage in this behaviour.Just over half (53% (95% CI 50.5% to 56.7%)) the respondents reported oral OTC analgesic use at least once in the previous month.In terms of medicine disposal, 29.3% (95% CI 26.6% to 32.2%) of respondents considered waste bin disposal to be of low or no harm., Conclusions: This study identified low levels of information-seeking and advice-seeking from pharmacy personnel especially on receipt of new prescription medicines. Potentially unsafe behaviours were identified in the use and disposal of medicines. These results will inform the development of interventions to promote advice-seeking and increase awareness regarding safe medicine use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Poor outcomes are common in individuals with anxiety and depression, and the brain circuits underlying symptoms and treatment responses remain elusive. To elucidate these neural circuits, experimental studies must specifically manipulate them, which is only possible in animals. Here, we used a chemogenetics strategy involving engineered designer receptors exclusively activated by designer drugs (DREADDs) to activate a region of the marmoset brain that is dysfunctional in human patients with major depressive disorder, called the subcallosal anterior cingulate cortex area 25 (scACC-25). Using this DREADDs system, we identified separate scACC-25 neural circuits that underlie specific components of anhedonia and anxiety in marmosets. Activation of the neural pathway connecting the scACC-25 to the nucleus accumbens (NAc) caused blunting of anticipatory arousal (a form of anhedonia) in marmosets in response to a reward-associated conditioned stimulus in an appetitive Pavlovian discrimination test. Separately, activation of the circuit between the scACC-25 and the amygdala increased a measure of anxiety (the threat response score) when marmosets were presented with an uncertain threat (human intruder test). Using the anhedonia data, we then showed that the fast-acting antidepressant ketamine when infused into the NAc of marmosets prevented anhedonia after scACC-25 activation for more than 1 week. These neurobiological findings provide targets that could contribute to the development of new treatment strategies.

Features of the airway microbiome in persons with cystic fibrosis (pwCF) are correlated with disease progression. Microbes have traditionally been classified for their ability to tolerate oxygen. It is unknown whether supplemental oxygen, a common medical intervention, affects the airway microbiome of pwCF. We hypothesized that hyperoxia significantly impacts the pulmonary microbiome in cystic fibrosis. In this study, we cultured spontaneously expectorated sputum from pwCF in artificial sputum medium under 21%, 50%, and 100% oxygen conditions using a previously validated model system that recapitulates microbial community composition in uncultured sputum. Culture aliquots taken at 24, 48, and 72 h, along with uncultured sputum, underwent shotgun metagenomic sequencing with absolute abundance values obtained with the use of spike-in bacteria. Raw sequencing files were processed using the bioBakery pipeline to determine changes in taxonomy, predicted function, antimicrobial resistance genes, and mobile genetic elements. Hyperoxia reduced absolute microbial load, species richness, and diversity. Hyperoxia reduced absolute abundance of specific microbes, including facultative anaerobes such as Rothia and some Streptococcus species, with minimal impact on canonical CF pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus. The effect size of hyperoxia on predicted functional pathways was stronger than that on taxonomy. Large changes in microbial cooccurrence networks were noted. Hyperoxia exposure perturbs airway microbial communities in a manner well tolerated by key pathogens. Supplemental oxygen use may enable the growth of lung pathogens and should be further studied in the clinical setting. IMPORTANCE The airway microbiome in persons with cystic fibrosis (pwCF) is correlated with lung function and disease severity. Supplemental oxygen use is common in more advanced CF, yet its role in perturbing airway microbial communities is unknown. By culturing sputum samples from pwCF under normal and elevated oxygen conditions, we found that increased oxygen led to reduced total numbers and diversity of microbes, with relative sparing of common CF pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus. Supplemental oxygen use may enable the growth of lung pathogens and should be further studied in the clinical setting.

Substantial progress has been made studying morphological changes in brain regions during adolescence, but less is known of network-level changes in their relationship. Here, we compare covariance networks constructed from the correlation of morphometric volumes across 135 brain regions of marmoset monkeys in early adolescence and adulthood. Substantial shifts are identified in the topology of structural covariance networks in the prefrontal cortex (PFC) and temporal lobe. PFC regions become more structurally differentiated and segregated within their own local network, hypothesized to reflect increased specialization after maturation. In contrast, temporal regions show increased inter-hemispheric covariances that may underlie the establishment of distributed networks. Regionally selective coupling of structural and maturational covariance is revealed, with relatively weak coupling in transmodal association areas. The latter may be a consequence of continued maturation within adulthood, but also environmental factors, for example, family size, affecting brain morphology. Advancing our understanding of how morphological relationships within higher-order brain areas mature in adolescence deepens our knowledge of the developing brain's organizing principles., (© The Author(s) 2022. Published by Oxford University Press.)

Structural and functional abnormalities of the orbitofrontal cortex (OFC) have been implicated in affective disorders that manifest anxiety-related symptoms. However, research into the functions of primate OFC has predominantly focused on reward-oriented rather than threat-oriented responses. To redress this imbalance, the present study performed a comprehensive analysis of the independent role of 2 distinct subregions of the central OFC (anterior area 11; aOFC and posterior area 13; pOFC) in the processing of distal and proximal threat. Temporary inactivation of both aOFC and pOFC heightened responses to distal threat in the form of an unknown human, but not to proximal threat assessed in a discriminative Pavlovian conditioning task. Inactivation of the aOFC, however, did unexpectedly blunt conditioned threat responses, although the effect was not valence-specific, as conditioned appetitive responses were similarly blunted and appeared restricted to a discriminative version of the task (when both CS- and CS+ are present within a session). Inactivation of the pOFC did not affect conditioned responses to either proximal threat or reward and basal cardiovascular activity was unaffected by manipulations of activity in either subregion. The results highlight the contribution of aOFC and pOFC to regulation of responses to more distal uncertain but not proximal, certain threat and reveal their opposing contribution to that of the immediately adjacent medial OFC, area 14., (© The Author(s) 2021. Published by Oxford University Press.)

Containing antimicrobial resistance and reducing high levels of antibiotic consumption in low- and lower middle-income countries are a major challenge. Clinical guidelines targeting antibiotic prescribing can reduce consumption, however, the degrees to which clinical guidelines are adopted and adhered to are challenging for developers, policy makers and users. The aim of this study was to review the strategies used for implementing and promoting antibiotic guideline adherence in low- and lower middle-income countries. A review of published literature was conducted using PubMed, Cochrane Library, SCOPUS and the information systems of the World Health Organization and the Australian National University according to PRISMA guidelines and our PROSPERO protocol. The strategies were grouped into five broad categories based on the Cochrane Effective Practice and Organization of Care taxonomy. The 33 selected studies, representing 16 countries varied widely in design, setting, disease focus, methods, intervention components, outcomes and effects. The majority of interventions were multifaceted and resulted in a positive direction of effect. The nature of the interventions and study variability made it impossible to tease out which strategies had the greatest impact on improving CG compliance. Audit and feedback coupled with either workshops and/or focus group discussions were the most frequently used intervention components. All the reported strategies are established practices used in antimicrobial stewardship programs in high-income countries. We recommend interrupted time series studies be used as an alternative design to pre- and post-intervention studies, information about the clinical guidelines be made more transparent, and prescriber confidence be investigated.

Background: Pacific Island countries, many of which are low- and middle-income countries, have some of the highest rates of diet-related non-communicable diseases (DR-NCDs) globally. These countries also face some of the earliest and most significant impacts of climate change. Several pathways between climate change and DR-NCDs have been described in the literature; however, the scope is broad and lacks context specificity. This paper uses a case study of one Pacific Island country, Vanuatu, to investigate links between climate change and DR-NCDs., Methods: An ethnographic qualitative research approach was used to share the lived experiences of community participants and to explore and contrast these with the perspectives of key informants at the national level. Data collection comprised thirty-two semi-structured interviews and community fieldwork in two villages using a mix of methods, including group workshops, informal conversations, and observations. Reflexive thematic analysis was conducted on both data sets., Results: This study found that DR-NCDs are a prominent health concern for ni-Vanuatu people and that structural determinants, including climate change, are the main driving forces for increased DR-NCD risk in the country. However, there was a lack of understanding of the links between climate change and DR-NCDs both at the community and national levels. Structural factors, such as social determinants and climate change, constrained individual and community agency in making optimal food and health choices and promoted the nutrition transition in Vanuatu. Despite the critical role of social determinants and climate change in driving DR-NCD risk, the responsibility for prevention and treatment was considered to rest mainly with the individual. A systems approach is advocated to grasp the complexity and interrelatedness of the causes of DR-NCD risk., Conclusions: The interaction of structural determinants creates food and health environments that amplify the risk, burden, and consequences of DR-NCDs. It is recommended that the DR-NCD narrative in Vanuatu be re-framed with an emphasis on the range of structural determinants of DR-NCD risk. This will serve to enhance individual and collective agency to not only make healthy food and other behavioural choices but also to exercise agency to transform the structures in a culturally appropriate way.

Dramatic shifts are occurring in the size, shape and skill of rural health workforces in Pacific island countries (PICs) due to an unprecedented convergence of political agreement, policy commitment, donor support and technical assistance. In particular, the impact of "medical internationalism" is being felt across the Pacific region, with new doctors returning home in far greater numbers than ever before, the majority having graduated from medical schools in Cuba, China and other countries outside the region, in addition to the more typical numbers graduating and returning home from the region's main medical schools in Fiji and Papua New Guinea. With an agreed regional vision of "Healthy Islands" across the Pacific, the main objective of expanding overseas training opportunities for Pacific island medical students has been to correct the widespread centralization and maldistribution of the medical workforce in PICs and improve health access and quality of care in rural areas by deploying the new graduates to outer-island facilities. However, the return of these new graduates in several PICs has demonstrated that additional training is required to equip them with the knowledge and skills necessary to practice safely and sustainably in unsupervised settings. Thus, the development of specific postgraduate programmes has been urgently needed to provide pathways to vocational training and specialization in rural medicine appropriate to the Pacific region. Rocketship Pacific Ltd. (Rocketship) is an international health charity, based in Australia, dedicated to improving health in Pacific island countries through stronger primary care. Rocketship's particular focus to date has been on education and capacity-building for doctors and nurses working in rural communities and outer-island facilities. Since 2015, Rocketship has been working in partnership with the Ministries of Health and other key partners in Solomon Islands, Timor-Leste, Tonga and Vanuatu to design and deliver postgraduate training programmes in the core generalist disciplines family, community and rural hospital medicine. To date, this has resulted in new postgraduate Family Medicine courses being established in Timor-Leste and Tonga; a rural medical workforce support programme being delivered in Vanuatu; and a new Postgraduate Diploma in Rural Generalist Medicine being designed in Solomon Islands. These new programmes, as well as other notable initiatives elsewhere in the Pacific such as the Master of Medicine (Rural) programme in Papua New Guinea, the Diploma and Master of Family Medicine programme in Fiji and the Cook Islands Fellowship in General Practice, are transforming the health workforce in PICs with the potential to benefit island people across the "Blue Continent." This paper describes the establishment of new postgraduate training programmes in family, community and rural hospital medicine in Timor-Leste, Tonga, Solomon Islands and Vanuatu from the perspective of Rocketship, the non-profit organization engaged by each country's Ministry of Health (or equivalent) to provide expert technical assistance with their initiative., Competing Interests: LM, DM, and L'U currently, or have been SJ, unpaid volunteers for the international health non-profit organization Rocketship Pacific Ltd., including in their respective capacities as pro-bono directors on the Board. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 McIver, Manahan, Jones and 'Ulufonua.)

Stress-related disorders such as depression and anxiety are characterized by enhanced negative emotion and physiological dysfunction. Whilst elevated activity within area 25 of the subgenual anterior cingulate cortex (sgACC/25) has been implicated in these illnesses, it is unknown whether this over-activity is causal. By combining targeted intracerebral microinfusions with cardiovascular and behavioral monitoring in marmosets, we show that over-activation of sgACC/25 reduces vagal tone and heart rate variability, alters cortisol dynamics during stress and heightens reactivity to proximal and distal threat. 18 F-FDG PET imaging shows these changes are accompanied by altered activity within a network of brain regions including the amygdala, hypothalamus and dorsolateral prefrontal cortex. Ketamine, shown to have rapid antidepressant effects, fails to reverse elevated arousal to distal threat contrary to the beneficial effects we have previously demonstrated on over-activation induced reward blunting, illustrating the symptom-specificity of its actions.

The ventromedial prefrontal cortex (vmPFC) is a key brain structure implicated in mood and anxiety disorders, based primarily on evidence from correlational neuroimaging studies. Composed of a number of brain regions with distinct architecture and connectivity, dissecting its functional heterogeneity will provide key insights into the symptomatology of these disorders. Focusing on area 14, lying on the medial and orbital surfaces of the gyrus rectus, this study addresses a key question of causality. Do changes in area 14 activity induce changes in threat- and reward-elicited responses within the nonhuman primate, the common marmoset, similar to that seen in mood and anxiety disorders? Area 14 overactivation was found to induce heightened responsivity to uncertain, low-imminence threat while blunting cardiovascular and behavioral anticipatory arousal to high-value food reward. Conversely, inactivation enhanced the arousal to high-value reward cues while dampening the acquisition of cardiovascular and behavioral responses to a Pavlovian threat cue. Basal cardiovascular activity, including heart rate variability and sympathovagal balance, which are dysfunctional in mood and anxiety disorders, are insensitive to alterations in area 14 activity as is the extinction of conditioned threat responses. The distinct pattern of dysregulation compared to neighboring region area 25 highlights the heterogeneity of function within vmPFC and reveals how the effects of area 14 overactivation on positive and negative reactivity mirror symptoms of anhedonia and anxiety that are so often comorbid in mood disorders., Competing Interests: The authors declare no competing interest.

People with obesity commonly face a pervasive, resilient form of social stigma. They are often subject to discrimination in the workplace as well as in educational and healthcare settings. Research indicates that weight stigma can cause physical and psychological harm, and that affected individuals are less likely to receive adequate care. For these reasons, weight stigma damages health, undermines human and social rights, and is unacceptable in modern societies. To inform healthcare professionals, policymakers, and the public about this issue, a multidisciplinary group of international experts, including representatives of scientific organizations, reviewed available evidence on the causes and harms of weight stigma and, using a modified Delphi process, developed a joint consensus statement with recommendations to eliminate weight bias. Academic institutions, professional organizations, media, public-health authorities, and governments should encourage education about weight stigma to facilitate a new public narrative about obesity, coherent with modern scientific knowledge.

Background: There is an acknowledged lack of robust and rigorous research focusing on the perspectives of those prescribing direct acting oral anticoagulants (DOACs) for non-valvular atrial fibrillation (AF)., Objective: The objective was to describe prescribers' experiences of using DOACs in the management of non-valvular AF, including perceptions of benefits and limitations., Methods: A cross-sectional survey of prescribers in a remote and rural area of Scotland. Among other items, the questionnaire invited free-text description of positive and negative experiences of DOACs, and benefits and limitations. Responses were independently analysed by two researchers using a summative content analysis approach. This involved counting and comparison, via keywords and content, followed by interpretation and coding of the underlying context into themes., Results: One hundred and fifty-four responses were received, 120 (77.9%) from physicians, 18 (11.7%) from nurse prescribers and 10 (6.4%) from pharmacist prescribers (6 unidentified professions). Not having to monitor INR was the most cited benefit, particularly for prescribers and patients in remote and rural settings, followed by potentially improved patient adherence. These benefits were reflected in respondents' descriptions of positive experiences and patient feedback. The main limitations were the lack of reversal agents, cost and inability to monitor anticoagulation status. Many described their experiences of adverse effects of DOACs including fatal and non-fatal bleeding, and upper gastrointestinal disturbances., Conclusions: While prescribers have positive experiences and perceive benefits of DOACs, issues such as adverse effects and inability to monitor anticoagulation status merit further monitoring and investigation. These issues are particularly relevant given the trajectory of increased prescribing of DOACs., Competing Interests: CONFLICT OF INTEREST The authors declare that they have no conflict of interest., (Copyright: © Pharmacy Practice.)

Keywords: drug resistance; antimicrobial; public health surveillance; Pacific Islands; bacteriology; epidemiology., Competing Interests: The authors declare no conflict of interest.

Human studies with self-reported measures have suggested a link between an avoidant coping style and high anxiety. Here, using the common marmoset as a model, we characterize the latent factors underlying behavioral responses of these monkeys towards low and high imminence threat and investigate if a predominantly avoidant behavioral response to high imminence threat is associated with greater anxiety-like behavior in a context of low imminence threat. Exploratory factor analysis (EFA) of the human intruder test of low imminence threat revealed a single factor in which a combination of active vigilance and avoidance responses underpinned anxiety-like behavior. In contrast, two negatively-associated factors were revealed in the model snake test reflecting active and avoidant coping to high imminence threat. Subsequent analysis showed that animals with a predominantly avoidant coping style on the model snake test displayed higher anxiety-like behavior on the human intruder test, findings consistent with those described in humans. Together they illustrate the richness of the behavioral repertoire displayed by marmosets in low and high imminence threatening contexts and the additional insight that factor analysis can provide by identifying the latent factors underlying these complex behavioral datasets. They also highlight the translational value of this approach when studying the neural circuits underlying complex anxiety-like states in this primate model., (Copyright © 2020 Quah, Cockcroft, McIver, Santangelo and Roberts.)

Background: Severe febrile illness without a known source (SFWS) is a challenge for clinicians when deciding how to manage a patient, particularly given the wide spectrum of potential aetiologies that contribute to fever. These infections are difficult to distinguish clinically, and accurate diagnosis requires a plethora of diagnostics including blood cultures, imaging techniques, molecular or serological tests, and more. When laboratory services are available, a limited test menu hinders clinical decision-making and antimicrobial stewardship, leading to empiric treatment and suboptimal patient outcomes. To specifically address SFWS, this work aimed to identify priority pathogens for a globally applicable panel for fever causing pathogens., Method: A pragmatic two-pronged approach combining currently available scientific data in an analytical hierarchy process and systematically gathered expert input, was designed to address the lack of comprehensive global aetiology data. The expert re-ranked list was then further adapted for a specific use case to focus on community acquired infections in whole blood specimens. The resulting list was further analysed to address different geographical regions (Asia, Africa, and Latin America), and Cohen kappa scores of agreement were calculated., Results: The expert ranked prioritized pathogen list generated as part of this two-pronged approach included typhoidal Salmonella, Plasmodium species and Mycobacterium tuberculosis as the top 3 pathogens. This pathogen list was then further adapted for the SFWS use case to develop a final pathogen list to inform product development. Subsequent analysis comparing the relevance of the SFWS pathogen list to multiple populations and geographical regions showed that the SFWS prioritized list had considerable utility across Africa and Asia, but less so for Latin America. In addition, the list showed high levels of agreement across different patient sub-populations, but lower relevance for neonates and symptomatic HIV patients., Conclusion: This work highlighted once again the challenges of prioritising in global health, but it also shows that taking a two-pronged approach, combining available prevalence data with expert input, can result in a broadly applicable priority list. This comprehensive utility is particularly important in the context of product development, where a sufficient market size is essential to achieve a sustainable commercialized diagnostic product to address SFWS.

Aims: A recent systematic review highlighted the lack of robust studies on prescribers' perspectives of direct-acting oral anticoagulants (DOACs) for nonvalvular atrial fibrillation. The aim was to determine prescribers' views and experiences of prescribing DOACs., Methods: A cross-sectional survey of prescribers in a remote and rural area of Scotland. Survey items were: demographics; prescribing of DOACs; views of potential influences on DOAC prescribing; knowledge of prescribing guidelines; and experiences. Items on potential influences were based on the Theoretical Domains Framework. Data were analysed using descriptive and inferential statistics, and content analysis of responses to open questions. Principal component analysis was performed on the items of potential influences., Results: In total, 154 responses were received, 120 (77.9%) from doctors, 18 (11.7%) from nurse prescribers and 10 (6.4%) from pharmacist prescribers (6 missing). Principal component analysis of the Theoretical Domains Framework items of potential influences gave 4 components. Component scores for (i) role of professionals, their knowledge and skills and (ii) influences on prescribing were positive. Those for (iii) consequences of prescribing and (iv) monitoring for safety and effectiveness were more neutral. There were low levels of agreement for statements relating to DOACs being more effective, safer and cost-effective than warfarin. There were similar responses around the complexity of bleeding management and detection of over and under-anticoagulation., Conclusion: This study has identified several key issues of DOAC prescribing (e.g. bleeding management) hence further emphasis is required in continuing professional development and during guideline implementation and evaluation., (© 2019 The British Pharmacological Society.)

Background: Snakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality antivenoms. This review aimed to systematically collect and analyse the clinical data on all antivenom products now available in markets of sub-Saharan Africa., Methodology/principal Findings: Our market analysis identified 12 polyspecific and 4 monospecific antivenom products in African markets. Our search strategy was first based on a systematic search of publication databases, followed by manual searches and discussions with experts. All types of data, including programmatic data, were eligible. All types of publications were eligible, including grey literature. Cohorts of less than 10 patients were excluded. 26 publications met the inclusion criteria. Many publications had to be excluded because clinical outcomes were not clearly linked to a specific product. Our narrative summaries present product-specific clinical data in terms of safety and effectiveness against the different species and envenoming syndromes. Three products (EchiTabPlus, EchiTabG, SAIMR-Echis-monovalent) were found to have been tested in robust clinical studies and found effective against envenoming caused by the West African carpet viper (Echis ocellatus). Four products (Inoserp-Panafricain, Fav-Afrique, SAIMR-Polyvalent, Antivipmyn-Africa) were found to have been evaluated only in observational single-arm studies, with varying results. For nine other products, there are either no data in the public domain, or only negative data suggesting a lack of effectiveness., Conclusions/significance: Clinical data vary among the different antivenom products currently in African markets. Some products are available commercially although they have been found to lack effectiveness. The World Health Organization should strengthen its capacity to assess antivenom products, support antivenom manufacturers, and assist African countries and international aid organizations in selecting appropriate quality antivenoms., Competing Interests: The authors have declared that no competing interests exist.