The application of tribology in assessing texture perception of oral liquid medicines

The palatability of medicines is likely to have a significant impact on patient adherence and consequently, on the safety and efficacy of a medicinal product. Palatability encompasses properties of medicines not limited to taste including swallowability (e.g. size, shape, texture). However, there has been limited work undertaken to measure the texture of medicines and how this may affect palatability and subsequent adherence. Tribology offers an understanding of oral processes and can allow physical properties of materials to be linked to "mouthfeel". This paper describes a preliminary application of tribology to oral liquid medicines and demonstrates that this technique is useful in the development of future oral liquid medicines

Developing consensus on the principles and key actions for collaborative working between general practices and community pharmacies: a modified eDelphi study

OBJECTIVES: To develop consensus on the principles and key actions for collaborative working in practice between general practice, community pharmacy and patients and their carers. DESIGN: Three-round modified eDelphi study, starting from an established conceptual model of collaboration between general practitioners (GPs) and community pharmacists. SETTING: Community pharmacies and general practices in England, UK. PARTICIPANTS: A panel of 123 experts: 43% from a community pharmacy background; 36% from a GP background; 13% patients, carers or patient representatives and 8% from academic or commissioner backgrounds. Panellist numbers reduced by approximately 30% in rounds 2 and 3. PRIMARY AND SECONDARY OUTCOME MEASURES: Consensus between expert panellists, defined as at least 75% agreement. RESULTS: A high level of consensus (>80%) was achieved on all components of a model of collaboration composed of Fundamental Principles of Collaboration and Key Activities for Action, supported by a series of aspirational statements and suggested practical actions. The fundamental principles and key activities are appended by contextual points. The findings indicate that collaboration in practice involves team members other than just GPs and community pharmacists and recognises that patients often want to know how each professional team is involved in their care. This study also provides insights into how collaboration between general practice and community pharmacy settings appears to have shifted during the COVID-19 pandemic, especially through opportunities for virtual collaboration and communication that can transcend the need for close geographical proximity. CONCLUSION: A consensus-based model of collaboration between general practice teams, community pharmacy teams, and patients and their carers has been developed. It is practically focused, values the patient voice and incorporates general practice and community pharmacy team members. While developed in England, the model is likely to also have applicability to other countries with similar health systems that include general practices and community pharmacies

Evaluating associations between metabolic health, obesity and depressive symptoms : a prospective analysis of data from the English Longitudinal Study of Ageing (ELSA) with a 2-year follow-up

OBJECTIVES: Conflicting results have been reported when the associations between metabolic health, obesity and depression were examined previously. The primary aim of this study was to determine whether metabolic health or obesity are independently associated with depressive symptoms, among a representative sample of older people living in England. Independent associations between covariates and depression were also examined. DESIGN: Prospective study with a 2-year follow-up. SETTING: The English Longitudinal Study of Ageing Wave 6 (2012-2013) and Wave 7 (2014-2015). PARTICIPANTS: 6804 participants aged older than 50 years. DATA ANALYSIS: Multivariate models were used to determine whether metabolic health or obesity are independently associated with depressive symptoms at 2-year follow-up. Unadjusted and adjusted ORs with corresponding 95% CI were calculated; the adjusted ORs took account of baseline depression, gender, age, wealth, obesity and poor metabolic health. RESULTS: Before adjusting for covariates, poor metabolic health was associated with depressive symptoms at 2-year follow-up (OR 1.24; 95% CI, 1.07 to 1.44, p<0.01). After adjusting for covariates, the association was no longer statistically significant (OR 1.17; 95% CI, 0.99 to 1.38, p=0.07). Similarly, obesity was associated with depressive symptoms at 2-year follow-up before adjusting for covariates (OR 1.54; 95% CI, 1.33 to 1.79, p<0.01). However, after adjusting for covariates the association between obesity and depressive symptoms at 2-year follow-up became statistically insignificant (OR 1.19; 95% CI, 1.00 to 1.41, p=0.06). The strongest predictors for future depression were baseline depression (OR 10.59; 95% CI, 8.90 to 12.53, p<0.01) and lower wealth (OR 3.23; 95% CI, 2.44 to 4.35, p<0.01). CONCLUSION: Neither poor metabolic health nor obesity were associated with a risk of depressive symptoms at 2-year follow-up, after adjusting for covariates. As wealth inequalities continue to rise across England, the risk of depressive symptoms at 2-year follow-up is likely to be elevated in individuals living in the lower wealth quintiles

Rheumatoid arthritis - clinical aspects: 134. Predictors of Joint Damage in South Africans with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA. Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value <0.05 was considered significant. Results: The mean (SD) age was 56 (9.8) years, disease duration 17.5 (8.5) years, educational level 7.5 (3.5) years and DMARD lag was 9 (8.8) years. Female to male ratio was 10:1. The mean (SD) DAS28 was 4.9 (1.5) and total RAAD score was 28.3 (12.8). The mean (SD) BMI was 27.2 kg/m2 (6.2) and 93% of patients were rheumatoid factor (RF) positive. More than 90% of patients received between 2 to 3 DMARDs. Significant univariate predictors of a poor RAAD score were increasing age (p = 0.001), lower education level (p = 0.019), longer disease duration (p < 0.001), longer DMARD lag (p = 0.014), lower BMI (p = 0.025), high RF titre (p < 0.001) and high ESR (p = 0.008). The multivariate regression analysis showed that the only independent significant predictors of a higher mean RAAD score were older age at disease onset (p = 0.04), disease duration (p < 0.001) and RF titre (p < 0.001). There was also a negative association between BMI and the mean total RAAD score (p = 0.049). Conclusions: Patients with longstanding established RA have more severe irreversible joint damage as measured by the clinical RAAD score, contrary to other studies in Africa. This is largely reflected by a delay in the initiation of early effective treatment. Independent of disease duration, older age at disease onset and a higher RF titre are strongly associated with more joint damage. The inverse association between BMI and articular damage in RA has been observed in several studies using radiographic damage scores. The mechanisms underlying this paradoxical association are still widely unknown but adipokines have recently been suggested to play a role. Disclosure statement: C.I. has received a research grant from the Connective Tissue Diseases Research Fund, University of the Witwatersrand. All other authors have declared no conflicts of interes

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Defining an ageing-related pathology, disease or syndrome: International Consensus Statement

Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand and meet the healthcare, workforce, well-being and socioeconomic needs of ageing populations, whilst supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies. The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19, 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥ 70% for approval. The accepted criteria for an ageing-related pathology, disease or syndrome were (1) develops and/or progresses with increasing chronological age; (2) should be associated with, or contribute to, functional decline or an increased susceptibility to functional decline and (3) evidenced by studies in humans. Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes

Determining the prevalence and nature of oral formulation-related barriers to medicines administration in paediatric patients suffering from chronic conditions

A systematic review identified limited studies exploring oral formulation-related barriers to medicines administration in children. Owing to the lack of licensed medicines suitable for use in children, manipulation is often required to deliver a specific dose or to facilitate medicines administration. Little is known regarding the prevalence and nature of issues encountered when administering medicines to children in the domiciliary setting. This study adopted a pragmatic approach to determine the nature and prevalence of oral formulation-related barriers to medicines administration in children suffering from a range of chronic conditions. Problems reported by healthcare professionals, patients and their parents/carers were identified to inform future pharmaceutical development and improve children’s medicines. Focus groups (n=4) were conducted with healthcare professionals in the West Midlands and semi-structured face-to-face interviews (n=278) were conducted with parents/carers/young people at University Hospitals Coventry and Warwickshire. Questions explored barriers to medicines administration, refusal and manipulation. In total, 31% of interview respondents reported medicines refusal. Taste was the most commonly reported barrier to medicines administration. Almost one fifth (19%) of medicines administered to children were reported to require manipulation. Findings indicate that age-appropriate medicines are required to provide both suitable dose units and acceptable taste for paediatric patients

The significance of ultrasound features of sub-chorionic haemorrhage as a predictor of adverse perinatal outcome: A retrospective review

Introduction This retrospective single centre study considers the predictive value of specific ultrasound features of sub-chorionic haemorrhage (SCH) as potential indicators of adverse pregnancy outcome. Methods Ultrasound reports and images were reviewed for 160 participants presenting to an early pregnancy assessment unit from January 2018 to January 2019. Participants were selected based upon the presence of SCH within the first trimester. The outcome of each pregnancy and the features of SCH, including the size, location and echogenicity were recorded and multinominal logistic regression was used to establish predictive value. Results The majority of participants were asymptomatic and delivered healthy babies. 24% miscarried prior to delivery or had stillborn babies; the features of bleed within this group revealed an increased prevalence of adverse outcome in the presence of moderate sized haemorrhage (p = 0.02). 61% of miscarried pregnancies presented with “wrapping” SCH, in which haemorrhage encased the gestation sac, suggesting wrapping posed a probable risk (p = 0.01). 71% of miscarriages occurred within 5 + 0–10 + 0 weeks gestation. Persistent SCH was of greater incidence within those participants with adverse outcome (57%). There was no association between fetal abnormality and miscarriage. Jaundice babies and premature delivery occurred more frequently (p = 0.001) and may be a secondary finding following SCH. Conclusion There was a strong correlation between presence of SCH in early pregnancy and rate of miscarriage. Specific ultrasound features of SCH, most notably a wrapping location with moderate size, may be indicative of increased risk of miscarriage or post-natal complications. Jaundice and premature births may have an association with placental compromise