Picker Institute Europe

Background Detection of bedaquiline (BDQ) resistance is essential for multidrug-resistant TB (MDR-TB) treatment. Mutations in mmpR5 (Rv0678), a transcriptional repressor of MmpL5/MmpS5 efflux pump, are the most frequent basis for clinical BDQ resistance, yet exhibit variable resistance. Current sequencing methods lack sensitivity and specificity due to the heterogeneity of resistance-associated variants (RAVs). We modeled conformational changes in MmpR5 RAVs and predict impact on protein stability, DNA binding, and phenotypic BDQ resistance. Methods A literature review identified mmpR5 genotype-phenotype correlations. We retrieved mmpR5 sequences and AlphaFold3 generated structural models with reference to solved crystal structure. Maestro was used to predict stability changes, while mCSM was applied to assess effects on MmpR5-DNA to evaluate association with minimum inhibitory concentrations (MICs) for BDQ. Results Structural changes in MmpR5 were observed across 3 RAV categories: low (Q22R, V85A, Y92fs), intermediate (G66E, M139fs), and high-level resistance (L142R, C46fs, M10fs). Maestro-predicted destabilization correlated with BDQ MICs. mCSM analysis revealed high-resistance mutations significantly impaired DNA binding affinity, potentially disrupting efflux pump repression. Conclusion Integrating structural analysis may enhance the predictive ability of targeted sequencing to predict phenotypic BDQ resistance. <fig><object-id>erj;66/suppl_69/PA788/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

BackgroundPatient and public voices are vital for understanding the quality of health and care. However, many healthcare providers, commissioners, decision-makers and researchers cannot hear the voices of all people within diverse populations, with different groups excluded from patient experience data collections and analyses for a variety of causes—some of which are overlooked or misunderstood. Exclusion and under-representation can be particularly problematic for disadvantaged people and marginalised communities, and risk exacerbating existing inequalities.Key messagesWe posit a taxonomy of causes of exclusion and under-representation in research involving patient and public voice: (1) Non-access: people are excluded because they cannot or do not access a service in the first place. (2) Non-invitation: health research and feedback programmes may not include invitations for some groups, despite being eligible, or use language that is inappropriate. (3) Non-response: some communities are less likely to respond to requests for feedback. (4) Non-identification: sometimes the structure and content of data do not allow the identification of distinct groups in data collections. (5) Non-review: sometimes data are available and yet not analysed. We provide a Toolkit for Assessing Under Representation in User Surveys to prompt conversations.ConclusionsThese causes result in under-representation that creates knowledge gaps for quality and equity. Overcoming this requires strategic approaches with a commitment to equity and inclusion, supported by resources in collecting and using data with an appropriate range of methodologies. Providers should undertake equalities impact assessments around new data collections, using the taxonomy to identify and minimise potential sources of under-representation and ensure that voices are heard and acted on.

Background: Integrated care systems (ICSs) in England were formally established in July 2022 to coordinate the planning and delivery of health and care services. A key responsibility was to address the quality of these services. Our study aimed to examine how ICSs approach this responsibility and to identify opportunities and barriers experienced in their early establishment and development.Methods: A sample of four ICSs were recruited to participate. Interviews and meeting observations were undertaken in two phases (before and after the inception of ICSs) around 12 months apart. A total of 112 interviews were carried out with senior figures in the four ICSs supplemented by observation of relevant meetings and analysis of relevant documents. Results: Regarding quality, ICSs demonstrated several new ways of working. They set-up new structures for quality governance and created whole-system strategies for quality centred on major responsibilities regarding population health and health inequalities. These strategies required new and relevant metrics to assess quality and outcomes and a greater focus upon co-production in the development of services. They aimed to strike a fine balance between long-standing requirements for quality assurance and new responsibilities for quality improvement (QI). New approaches were underpinned by new collaborations between system partners extending beyond healthcare to include Local Authorities (responsible for social care and public health) and local communities. Conclusion: To address the many challenges of quality, ICSs have created new ways of working cultivating different kinds of collaborative relationships compared to established hierarchical, siloed and top-down ways of working prior to their formation. A focus on improving population health and reducing inequalities has required a shift from "here and now" urgent problem-solving to working with longer timelines. Such changes require patience in the context of political pressure to devote efforts to more salient problems such as waiting lists.

To develop and explore the validity of a Patient Reported Experience Measure (PREM) for adult inpatient diabetes care. 27 in-depth interviews were conducted to inform the development of the 42-item PREM which was cognitively tested with 10 people. A refined 38-item PREM was piloted with 228 respondents completing a paper (n = 198) or online (n = 30) version. The performance of the PREM was evaluated by exploring (i) uptake/number of responses and (ii) survey validity by investigating whether the PREM data were of adequate quality and delivered useful information. The PREM had low drop-out or missing data rates suggesting it was appropriately constructed. Analysis of item frequencies and variances, and problem score calculations concluded that questions provided sufficient score differentiation. This new PREM allows for experiences of inpatient diabetes care to be measured, understood and reported on to help identify priority areas for improving care quality.

Background: Between 10% and 15% of hypothyroid patients experience persistent symptoms despite achieving biochemical euthyroidism. Unexplained persistent symptoms can be a sign of somatization. This is associated with distress and high health care resource use and can be classified as somatic symptom disorder (SSD). Prevalence rates for SSD differ depending on classification criteria and how they are ascertained, varying between 4% and 25%. As this has not been studied in hypothyroid patients before, the aim of this study was to document somatization in people with hypothyroidism and to explore associations with other patient characteristics and outcomes. Methods: Online, multinational cross-sectional survey of individuals with self-reported, treated hypothyroidism, which included the validated Patient Health Questionnaire-15 (PHQ-15) for assessment of somatization. Chi-squared tests with the Bonferroni correction were used to explore outcomes for respondents with a PHQ-15 score ≥10 (probable somatic symptom disorder [pSSD]) versus a PHQ-15 score <10 (absence of SSD). Results: A total of 3915 responses were received, 3516 of which contained the valid PHQ-15 data (89.8%). The median score was 11.3 (range 0-30 [confidence interval 10.9-11.3]). The prevalence of pSSD was 58.6%. Associations were found between pSSD and young age (p < 0.001), women (p < 0.001), not working (p < 0.001), having below average household income (p < 0.001), being treated with levothyroxine (LT4) (rather than combination of LT4 and L-triiodothyronine [LT3], LT3 alone, or desiccated thyroid extract) (p < 0.001), expression of the view that the thyroid medication taken did not control the symptoms of hypothyroidism well (p < 0.001), and with number of comorbidities (p < 0.001). pSSD was associated with respondent attribution of most PHQ-15 symptoms to the hypothyroidism or its treatment (p < 0.001), dissatisfaction with care and treatment of hypothyroidism (p < 0.001), a negative impact of hypothyroidism on daily living (p < 0.001), and with anxiety and low mood/depression (p < 0.001). Conclusions: This study demonstrates a high prevalence of pSSD among people with hypothyroidism and associations between pSSD and negative patient outcomes, including a tendency to attribute persistent symptoms to hypothyroidism or its treatment. SSD may be an important determinant of dissatisfaction with treatment and care among some hypothyroid patients.

Limited literature exists documenting mealtime challenges and evidence for early intervention for children with visual impairment (VI). The objective of this pilot study was to determine whether a mealtime routines intervention for children with VI from 6 to 24 months would affect food texture, variety, and healthy food choices. The intervention occurred in homes/childcare settings involving children with VI, their caretakers, and their early interventionists. The intervention group scored higher than the control group for acceptance of food textures at 6–24 months (p ≤ .005) and at 13–24 months (p ≤ .007) and for consuming a greater variety of foods between 6 and 12 months (p ≤ .04). Assessment scores for positive caregiver and child mealtime behaviors were higher for the intervention group, p = .0000. The intervention showed promise for enhancing positive mealtime behaviors, feeding skills, and food acceptance.

ABSTRACT The author lays out four key water-related priorities for the new Biden administration.

ObjectivesImproving patient experience is widely regarded as a key component of health care quality. However, while a considerable amount of data are collected about patient experience, there are concerns this information is not always used to improve care. This study explored whether and how frontline staff use patient experience data for service improvement.MethodsWe conducted a year-long ethnographic case study evaluation, including 299 hours of observations and 95 interviews, of how frontline staff in six medical wards at different hospital sites in the United Kingdom used patient experience data for improvement.ResultsIn every site, staff undertook quality improvement projects using a range of data sources. Teams of health care practitioners and ancillary staff engaged collectively in a process of sense-making using formal and informal sources of patient experience data. While survey data were popular, ‘soft’ intelligence – such as patients’ stories, informal comments and observations – also informed staff’s improvement plans, without always being recognized as data. Teams with staff from different professional backgrounds and grades tended to make more progress than less diverse teams, being able to draw on a wider net of practical, organizational and social resources, support and skills, which we describe as team-based capital.ConclusionsOrganizational recognition, or rejection, of specific forms of patient experience intelligence as ‘data’ affects whether staff feel the data are actionable. Teams combining a diverse range of staff generated higher levels of ‘team-based capital’ for quality improvement than those adopting a single disciplinary approach. This may be a key mechanism for achieving person-centred improvement in health care.