The Attitudes about Complex Therapy Scale (ACTS) in Type 2 Diabetes and Cardiovascular Disease: Development, Validity and Reliability

Background: Type 2 diabetes is associated with cardiovascular disease, and patients with both conditions are prescribed complex medication regimens. Aim: The aim was to develop a reliable and valid measure of attitudes associated with the prescription and management of multiple medicines in patients with Type 2 diabetes and cardiovascular disease. Methods: Principal component analysis (PCA) and Cronbach alpha assessed the reliability of the Attitudes about Complex Therapy Scale (ACTS). Examinations of relationships with related measures inform concurrent validity. Questionnaires were sent to a cross-sectional sample of 480 people prescribed multiple medicines for co-morbid Type 2 diabetes. Results: Cronbach alpha was 0.76, indicating the scale had good internal reliability. PCA rotated a four factor model accounting for 37% of the variance. Four subscales identified; 1. Concerns about multiple medicines and increasing numbers of medicines; 2.Anxiety over missed medicines; 3. Desires to substitute medicines and reduce the number of medicines prescribed and; 4. Perceptions related to organising and managing complex therapy. The ACTS showed significant relationships with measures of anxiety, depression, general beliefs about medicines and self-efficacy. Also, the ACTS significantly correlated with adherence to medicines, showing good predictive validity. Conclusion: The ACTS was designed to assess negative attitudes towards complex therapy and multiple medication management. This tool could aid prescribing decisions and may identify people who are intentionally non-adherent to all or some of their medicines

Healthcare professionals’ perceptions of risk in the context of genetic testing for the prediction of chronic disease: a qualitative metasynthesis

Advances in genomic technologies and a growing trend towards stratified and preventive approaches to medicine mean that increasing numbers of individuals may have access to information about their genetic makeup, and their risk of developing diseases. This is likely to impact on healthcare professionals involved in the delivery of genetic tests, or in supporting patients who are affected by a disease with a genetic risk factor. It is therefore important to understand health-care professionals’ perceptions about providing these services, and how they feel about communicating information about genetic risk to patients. This paper provides a systematic review and metasynthesis of qualitative research exploring healthcare professionals’ perceptions of genetic risk in the context of predictive genetic testing for chronic disease. Healthcare professionals expressed a range of reservations about the utility of predictive testing in this context. Professionals judged patients’ understanding of risk information to be limited and subject to bias and a range of sociocultural influences. Concerns about the psychosocial impact of genetic risk information were frequently cited, both in relation to individual patients and the wider impact on their families and communities. The need for provision of multidisciplinary support was described. The concept of responsibility was also an important theme. Healthcare professionals recognized the responsibility that accompanies risk knowledge, and that ultimately this responsibility lies with the patient, not the provider. Our analysis suggests that professionals’ evaluation of the utility of predictive genetic testing is influenced not only by resource deficits, but may also be interpreted as a response to challenging ethical and social issues associated with genetic risk, that are not well aligned with current medical practice

General practitioners’ perspectives on campaigns to promote rapid help-seeking behaviour at the onset of rheumatoid arthritis

Objective. To explore general practitioners’ (GPs’ ) perspectives on public health campaigns to encourage people with the early symptoms of rheumatoid arthritis (RA) to seek medical help rapidly. Design. Nineteen GPs participated in four semistructured focus groups. Focus groups were audio-recorded, transcribed verbatim, and analysed using thematic analysis. Results. GPs recognised the need for the early treatment of RA and identified that facilitating appropriate access to care was important. However, not all held the view that a delay in help seeking was a clinically significant issue. Furthermore, many were concerned that the early symptoms of RA were often non-specific, and that current knowledge about the nature of symptoms at disease onset was inadequate to inform the content of a help-seeking campaign. They argued that a campaign might not be able to specifically target those who need to present urgently. Poorly designed campaigns were suggested to have a negative impact on GPs’ workloads, and would “clog up” the referral pathway for genuine cases of RA. Conclusions. GPs were supportive of strategies to improve access to Rheumatological care and increase public awareness of RA symptoms. However, they have identified important issues that need to be considered in developing a public health campaign that forms part of an overall strategy to reduce time to treatment for patients with new onset RA. This study highlights the value of gaining GPs’ perspectives before launching health promotion campaigns

Patient perceptions of treatment and illness when prescribed multiple medicines for co-morbid type 2 diabetes

Illness and treatment perceptions are vital for people self-managing co-morbid conditions with associated cardiovascular disease, such as type 2 diabetes (T2D). However, perceptions of a co-morbid condition and the use of multiple medicines have yet to be researched. This study investigated the illness and treatment perceptions of people with co-morbid T2D. The Brief Illness Perception Questionnaire (repeated for T2D, hypertension, and hyperlipidemia) and the Beliefs about Medicines Questionnaire Specific Concerns Scales (repeated for Oral hypoglycemic agents, anti-hypertensive medicines, and statins) were sent to 480 people managing co-morbid T2D. Data on the number of medicines prescribed were collected from medical records. Significantly different perceptions were found across the illnesses. The strongest effect was for personal control; the greatest control reported for T2D. Illness perceptions of T2D differed significantly from perceptions about hyperlipidemia. Furthermore, illness perceptions of T2D also differed from perceptions of hypertension with the exception of perceptions of illness severity. Hypertension and hyperlipidemia shared similar perceptions about comprehensibility, concerns, personal control, and timeline. Significant differences were found for beliefs about treatment necessity, but no difference was found for treatment concerns. When the number of medicines was taken as a between-subjects factor, only intentional non-adherence, treatment necessity beliefs, and perceptions of illness timeline were accounted for. Co-morbid illness and treatment perceptions are complex, often vary between illnesses, and can be influenced by the number of medicines prescribed. Further research should investigate relationships between co-morbid illness and treatment perception structures and self-management practices

Screening the medicines for Malaria Venture "Malaria Box" against the Plasmodium falciparum aminopeptidases, M1, M17 and M18

Malaria is a parasitic disease that remains a global health burden. The ability of the parasite to rapidly develop resistance to therapeutics drives an urgent need for the delivery of new drugs. The Medicines for Malaria Venture have compounds known for their antimalarial ac- tivity, but not necessarily the molecular targets. In this study, we assess the ability of the “MMV 400” compounds to inhibit the activity of three metalloaminopeptidases from Plasmo- dium falciparum, PfA-M1, PfA-M17 and PfM18 AAP. We have developed a multiplex assay system to allow rapid primary screening of compounds against all three metalloaminopepti- dases, followed by detailed analysis of promising compounds. Our results show that there were no PfM18AAP inhibitors, whereas two moderate inhibitors of the neutral aminopepti- dases PfA-M1 and PfA-M17 were identified. Further investigation through structure-activity relationship studies and molecular docking suggest that these compounds are competitive inhibitors with novel binding mechanisms, acting through either non-classical zinc coordina- tion or independently of zinc binding altogether. Although it is unlikely that inhibition of PfA- M1 and/or PfA-M17 is the primary mechanism responsible for the antiplasmodial activity re- ported for these compounds, their detailed characterization, as presented in this work, pave the way for their further optimization as a novel class of dual PfA-M1/PfA-M17 inhibitors uti- lising non-classical zinc binding groups

Orbital fractures and concurrent ocular injury in a New Zealand tertiary centre

BackgroundOrbital fractures are a common presentation to acute care and carry an associated risk of ocular injury, however, previous research has not investigated injury rates by fracture category. These patients are frequently assessed by non-ophthalmic clinicians, however, limited data exists regarding referral patterns and how this impacts recorded injury rates (1–3).MethodsWe performed a retrospective review of all orbital fractures presenting to a tertiary hospital in Christchurch, New Zealand between March 2019 and March 2021. Data including mechanism of injury, fracture type, demographic characteristics, and associated ocular injury were recorded.Results284 patients with orbital fractures were identified. 41% of patients had isolated wall fractures, while 59% had complex orbitofacial fractures. Fractures were more common in males, and occurred more frequently in young individuals. The most common mechanism of injury was interpersonal violence (32%), followed by falls (23%). 41% of patients were reviewed by ophthalmology (n = 118). Of those, 33% had an associated ocular injury. Severe ocular injury (defined as vision threatening, requiring globe surgery or acute lateral canthotomy and cantholysis) occurred in 4.9% of those with formal ophthalmic review. 0.7% of patients required intraocular surgery or lateral canthotomy due to their orbital fracture.ConclusionOrbital fractures have a high rate of concurrent ocular injury in our study population, though rates of subsequent intraocular surgery are low. There was no significant difference in injury rates between isolated and complex fracture categories. Vision-threatening ocular injury occurred in 4.9% of fractures

A proteomic approach to investigating gene cluster expression and secondary metabolite functionality in Aspergillus fumigatus.

A combined proteomics and metabolomics approach was utilised to advance the identification and characterisation of secondary metabolites in Aspergillus fumigatus. Here, implementation of a shotgun proteomic strategy led to the identification of non-redundant mycelial proteins (n = 414) from A. fumigatus including proteins typically under-represented in 2-D proteome maps: proteins with multiple transmembrane regions, hydrophobic proteins and proteins with extremes of molecular mass and pI. Indirect identification of secondary metabolite cluster expression was also achieved, with proteins (n = 18) from LaeA-regulated clusters detected, including GliT encoded within the gliotoxin biosynthetic cluster. Biochemical analysis then revealed that gliotoxin significantly attenuates H2O2-induced oxidative stress in A. fumigatus (p>0.0001), confirming observations from proteomics data. A complementary 2-D/LC-MS/MS approach further elucidated significantly increased abundance (p<0.05) of proliferating cell nuclear antigen (PCNA), NADH-quinone oxidoreductase and the gliotoxin oxidoreductase GliT, along with significantly attenuated abundance (p<0.05) of a heat shock protein, an oxidative stress protein and an autolysis-associated chitinase, when gliotoxin and H2O2 were present, compared to H2O2 alone. Moreover, gliotoxin exposure significantly reduced the abundance of selected proteins (p<0.05) involved in de novo purine biosynthesis. Significantly elevated abundance (p<0.05) of a key enzyme, xanthine-guanine phosphoribosyl transferase Xpt1, utilised in purine salvage, was observed in the presence of H2O2 and gliotoxin. This work provides new insights into the A. fumigatus proteome and experimental strategies, plus mechanistic data pertaining to gliotoxin functionality in the organism

Development and formative evaluation of patient research partner involvement in a multi-disciplinary European translational research project

Patient and public involvement (PPI) improves the quality of health research and ensures that research is relevant to patients’ needs. Though PPI is increasingly evident in clinical and health services research, there are few examples in the research literature of effective PPI in translational and laboratory-based research. In this paper, we describe the development and evaluation of PPI in a multi-centre European project (EuroTEAM – Towards Early biomarkers in Arthritis Management) that included both translational and laboratory-based and psychosocial research. We found that although most PPI in EuroTEAM was centred around the psychosocial research, there were examples of PPI in the laboratory studies. As the project evolved, researchers became better at accommodating PPI and identifying PPI opportunities. It was generally agreed that PPI had a positive impact on the project overall, particularly on public engagement with the research. We concluded that the inclusion of both psychosocial and laboratory-based research in the same project facilitated PPI across all aspects of the research. In future projects, we would try to specify individual PPI activities in more detail at the project-planning stage, and better accommodate patient partners who are not native speakers of English. Background Patient and public involvement (PPI) enhances research quality and relevance and is central to contemporary health policy. The value of PPI has been recognised in rheumatology research, though there are limited examples of PPI in basic and translational science. The EU FP7 funded ‘EuroTEAM’ (Towards Early biomarkers in Arthritis Management) project was established to develop biomarker-based approaches to predict the future development of rheumatoid arthritis and incorporated psychosocial research to investigate the perceptions of ‘at risk’ individuals about predictive testing, and to develop informational resources about rheumatoid arthritis (RA) risk. Patient involvement was central to EuroTEAM from the inception of the project. The objective of this paper is to describe the development of PPI in EuroTEAM, formatively assess the impact of PPI from the perspectives of researchers and patient research partners (PRPs), reflect on successes and lessons learned, and formulate recommendations to guide future projects. Methods Two mixed-methods surveys (for PRPs and researchers) and a teleconference were undertaken to assess the impact of PPI on individual work packages and on EuroTEAM overall. Results There was consensus about the positive impact of PPI on the research and on the experiences of those involved. In particular, the positive impact of PPI on the personal development of researchers, and on effective public engagement with EuroTEAM research were highlighted. Researchers described adapting their practice in future projects to facilitate PPI. Spin-off projects and ongoing collaborations between PRPs and researchers reflected the value of PPI to participants. PPI was more frequently integrated in psychosocial research, though examples of PPI in laboratory/translational science were also described. PRPs asked for more opportunities to contribute meaningfully to basic scientific research and for more extensive feedback on their contributions. Conclusions The findings were used to formulate recommendations to guide effective involvement of patients in future similar projects, including identifying specific training requirements for PRPs and researchers, the identification of PRP focused tasks/deliverables at the project planning stage, and supporting access to involvement for all PRPs. Importantly, the distinctive multidisciplinary approach of EuroTEAM, incorporating both basic science and psychosocial research, facilitated patient involvement in the project overall

Overdose responses among rural people who use drugs: A multi-regional qualitative study

Background Efforts to distribute naloxone have equipped more people with the ability to reverse opioid overdoses but people who use drugs are often reluctant to call 911 due to concerns for legal repercussions. Rural communities face unique challenges in reducing overdose deaths compared to urban communities, including limited access to harm reduction services as well as greater concerns about stigma and privacy. Methods The Rural Opioid Initiative was funded in 2017 to better understand the health-related harms associated with the opioid crisis in rural US communities and consists of eight studies spanning ten states and 65 counties. Each study conducted semi-structured qualitative interviews with people who use drugs to understand contextual factors influencing drug use and health behaviors. We analyzed qualitative data from seven studies with data available at the time of analysis to understand peer response to overdose. Results Of the 304 participants interviewed, 55% were men, 70% were white, 80% reported current injection drug use, and 60% reported methamphetamine use. Similar to what has been found in studies focused on urban settings, people who use drugs in rural communities use a range of strategies to reverse overdoses, including non-evidence-based approaches. Several reported that multiple doses of naloxone are needed to reverse overdose. Three themes emerged around the willingness to call 911, including (1) hesitancy to call 911 for fear of legal consequences, (2) negative perceptions or experiences with law enforcement officers, and (3) efforts to obtain medical intervention while avoiding identification/law enforcement involvement. Conclusion People who use drugs employ multiple strategies to attempt overdose reversal, including non-evidence-based approaches. Greater education about the most effective and least harmful strategies is needed. Reluctance to call 911 is rooted in concerns about potential legal consequences as well as perceptions about law enforcement officers, which may be heightened in rural communities where people who use drugs are more easily identified by law enforcement. People who use drugs will go to great strides to connect their peers to needed medical services, suggesting that comprehensive interventions to reduce interactions with law enforcement officers and eliminate legal consequences for reporting overdoses are critical

Predictors of interest in predictive testing for rheumatoid arthritis among first degree relatives of rheumatoid arthritis patients

Objectives: There is increasing interest in prediction and prevention of RA. It is important to understand the views of those at risk to inform the development of effective approaches. First-degree relatives (FDRs) of RA patients are at increased risk of RA. This study assessed predictors of their interest in predictive testing for RA. Methods: Questionnaires were completed by RA patients (provided with their questionnaire by a healthcare professional) and their FDRs (provided with their questionnaire by their RA proband). FDR surveys assessed interest in taking a predictive test, demographic variables, perceived RA risk, attitudes about predictive testing, autonomy preferences, illness perceptions, avoidance coping and health anxiety. Patient surveys included demographic variables, disease impact, RA duration and treatment. Ordinal logistic regression examined the association between FDRs’ characteristics and their interest in predictive testing. Generalized estimating equations assessed associations between patient characteristics and FDRs’ interest in predictive testing. Results: Three hundred and ninety-six FDRs responded. Paired data from the RA proband were available for 292. The proportion of FDRs interested in predictive testing was 91.3%. Information-seeking preferences, beliefs that predictive testing can increase empowerment over health and positive attitudes about risk knowledge were associated with increased interest. Beliefs that predictive testing could cause psychological harm predicted lower interest. Patient characteristics of the proband were not associated with FDRs’ interest. Conclusions: FDRs’ interest in predictive testing for RA was high, and factors associated with interest were identified. These findings will inform the development of predictive strategies and informational resources for those at risk