Associative interference and nonreinforcement in human contingency learning.

This article reports three experiments comparing the impact on contingency assessment of associative cue interference (proactive, interspersed, and retroactive) and nonreinforcement (latent inhibition, partial reinforcement, and extinction). All three experiments used variants of the rapid trial streaming procedure developed by Allan and collaborators. Participants were exposed to stimulus streams and then asked how likely it was for a target cue to be accompanied (Experiment 1) or to be followed (Experiments 2 and 3) by a target outcome. Experiments 1 and 2 looked at interference and found that when the objective target cue-outcome contingency is positive, interspersed interference is more effective than either proactive or retroactive interference. Experiment 2 additionally showed that this conclusion was a function of the target cue-outcome contingency: when the number of cue-outcome pairings was low, retroactive interference was more efficient than interspersed interference. Experiment 3 examined nonreinforcement and found that the efficacies of latent inhibition, partial reinforcement, and extinction are also a function of the target cue-outcome contingency, but the pattern differed greatly from what was observed in Experiment 2. When the number of cue-outcome pairings was high, there was no difference between latent inhibition, partial reinforcement, and extinction. When the number of cue-outcome pairings was low, extinction did not lower the contingency judgement, whereas latent inhibition and partial reinforcement did.

Encouraging openness in health care: Policy and practice implications of a mixed-methods study in the English National Health Service.

OBJECTIVE: The National Health Service (NHS) in England has introduced a range of policy measures aimed at fostering greater openness, transparency and candour about quality and safety. We draw on the findings of an evaluation of the implementation of these policies in NHS organisations, with the aim of identifying key implications for policy and practice. METHODS: We undertook a mixed-methods policy evaluation, comprising four substudies: a longitudinal analysis of data from surveys of NHS staff and service users; interviews with senior stakeholders in NHS provider organisations and the wider system; a survey of board members of NHS provider organisations and organisational case studies across acute, community and mental health, and ambulance services. RESULTS: Our findings indicate a mixed picture of progress towards improving openness in NHS organisations, influenced by organisational history and memories of past efforts, and complicated by organisational heterogeneity. We identify four features that appear to be necessary conditions for sustained progress in improving openness: (1) authentic integration into organisational mission is crucial in making openness a day-to-day concern; (2) functional and effective administrative systems are vital; (3) these systems must be leavened by flexibility and sensitivity in implementation and (4) a spirit of continuous inquiry, learning and improvement is required to avoid the fallacy that advancing openness can be reduced to a time-limited project. We also identify four persistent challenges in consolidating and sustaining improvement: (1) a reliance on goodwill and discretionary effort; (2) caring for staff, patients and relatives who seek openness; (3) the limits of values-driven approaches on their own and (4) the continued marginality of patients, carers and families. CONCLUSIONS: Variation in policy implementation offers important lessons on how organisations can better deliver openness, transparency and candour. These lessons highlight practical actions for policymakers, managers and senior clinicians.

The Role of in silico Research in Developing Nanoparticle-Based Therapeutics.

Nanoparticles (NPs) hold great potential as therapeutics, particularly in the realm of drug delivery. They are effective at functional cargo delivery and offer a great degree of amenability that can be used to offset toxic side effects or to target drugs to specific regions in the body. However, there are many challenges associated with the development of NP-based drug formulations that hamper their successful clinical translation. Arguably, the most significant barrier in the way of efficacious NP-based drug delivery systems is the tedious and time-consuming nature of NP formulation-a process that needs to account for downstream effects, such as the onset of potential toxicity or immunogenicity, in vivo biodistribution and overall pharmacokinetic profiles, all while maintaining desirable therapeutic outcomes. Computational and AI-based approaches have shown promise in alleviating some of these restrictions. Via predictive modeling and deep learning, in silico approaches have shown the ability to accurately model NP-membrane interactions and cellular uptake based on minimal data, such as the physicochemical characteristics of a given NP. More importantly, machine learning allows computational models to predict how specific changes could be made to the physicochemical characteristics of a NP to improve functional aspects, such as drug retention or endocytosis. On a larger scale, they are also able to predict the in vivo pharmacokinetics of NP-encapsulated drugs, predicting aspects such as circulatory half-life, toxicity, and biodistribution. However, the convergence of nanomedicine and computational approaches is still in its infancy and limited in its applicability. The interactions between NPs, the encapsulated drug and the body form an intricate network of interactions that cannot be modeled with absolute certainty. Despite this, rapid advancements in the area promise to deliver increasingly powerful tools capable of accelerating the development of advanced nanoscale therapeutics. Here, we describe computational approaches that have been utilized in the field of nanomedicine, focusing on approaches for NP design and engineering.

The impact of Victorian COVID-19 lockdowns on the presentation and management of acute appendicitis.

BACKGROUNDS: The COVID-19 pandemic presents ongoing challenges for healthcare. Stay at Home orders ('lockdowns') and community fears have been suggested to create reluctance to seek healthcare. We aimed to determine whether the rates of perforated appendicitis and negative appendicectomy have been affected by the pandemic, and to analyse the effect of lockdowns on the management of acute appendicitis in Victoria. METHODS: We conducted a retrospective audit of emergency appendicectomies performed under adult General Surgery units at Monash Health in Victoria from January 2019 to September 2021, including 242 days of lockdown. RESULTS: 2459 patients were included. Fewer patients had perforated appendicitis during the second lockdown (6.3% versus 10.7% baseline; p = 0.027). The rate of negative appendicectomy was reduced during the first lockdown (4.1% versus 14.9% baseline; p = 0.002) and during intervals between lockdown in 2021 (9.8%; p = 0.010). There was no difference in the rate of perforated appendicitis or negative appendicectomy at other times. Time to surgery and number of appendicectomies performed were also not significantly different. Fewer appendicectomies were performed after hours during lockdowns and in 2021 more generally compared to baseline (p < 0.05). CONCLUSION: The lower negative appendicectomy rate during the first lockdown may reflect increased pre-operative imaging or clinical observation for undifferentiated presentations. There was a reduction in perforated appendicitis during the second lockdown, and no significant difference at other times. Contrary to other studies, lockdowns associated with the COVID-19 pandemic may not create a reluctance to seek healthcare in all regions.

Why do systems for responding to concerns and complaints so often fail patients, families and healthcare staff? A qualitative study.

Healthcare organisations' responses to concerns and complaints often fall short of the expectations of patients and staff who raise them, and substandard responses to concerns and complaints have been implicated in organisational failures. Informed by Habermas's systems theory, we offer new insights into the features of organisations' responses to concerns and complaints that give rise to these problems. We draw on a large qualitative dataset, comprising 88 predominantly narrative interviews with people raising and responding to concerns and complaints in six English NHS organisations. In common with past studies, many participants described frustrations with systems and processes that seemed ill-equipped to deal with concerns of the kinds they raised. Departing from existing analyses, we identify the influence of functional rationality, as conceptualised by Habermas, and embodied in procedures, pathways and scripts for response, in producing this dissatisfaction. Functionally rational processes were well equipped to deal with simple, readily categorised concerns and complaints. They were less well placed to respond adequately to concerns and complaints that were complex, cross-cutting, or irreducible to predetermined criteria for redress and resolution. Drawing on empirical examples and on Habermas's theory of communicative action, we offer suggestions for alternative and supplementary approaches to responding to concerns and complaints that might better address both the expectations of complainants and the improvement of services.

Uncovering, creating or constructing problems? Enacting a new role to support staff who raise concerns about quality and safety in the English National Health Service.

Employee voice is an important source of organizational intelligence about possible problems in quality and patient safety, but effective systems for encouraging and supporting those who seek to speak up have remained elusive. In the English National Health Service, a novel role known as the 'Freedom to Speak Up Guardian' has been introduced to address this problem. We critically examine the role and its realization in practice, drawing on semi-structured interviews with 51 key individuals, including Guardians, clinicians, managers, policymakers, regulators and others. Operationalizing the new role in organizations was not straightforward, since it had to sit in a complex set of existing systems and processes. One response was to seek to bound the scope of Guardians, casting them in a signposting or coordinating role in relation to quality and safety concerns. However, the role proved hard to delimit, not least because the concerns most frequently voiced in practice differed in character from those anticipated in the role's development. Guardians were tasked with making sense of and dealing with issues that could not always straightforwardly be classified, deflected to the right system or escalated to the appropriate authority. Our analysis suggests that the role's potential contribution might be understood less as supporting whistleblowers who bear witness to clear-cut wrongdoing, and more as helping those with lower-level worries to construct their concerns and what to do with them. These findings have implications for how voice is understood, imagined and addressed in healthcare organizations.

A qualitative study of design stakeholders' views of developing and implementing a registry-based learning health system.

BACKGROUND: New opportunities to record, collate, and analyze routine patient data have prompted optimism about the potential of learning health systems. However, real-life examples of such systems remain rare and few have been exposed to study. We aimed to examine the views of design stakeholders on designing and implementing a US-based registry-enabled care and learning system for cystic fibrosis (RCLS-CF). METHODS: We conducted a two-phase qualitative study with stakeholders involved in designing, implementing, and using the RCLS-CF. First, we conducted semi-structured interviews with 19 program personnels involved in design and delivery of the program. We then undertook 11 follow-up interviews. Analysis of interviews was based on the constant comparative method, supported by NVivo software. RESULTS: The organizing principle for the RCLS-CF was a shift to more partnership-based relationships between patients and clinicians, founded in values of co-production, and facilitated by technology-enabled data sharing. Participants proposed that, for the system to be successful, the data it collects must be both clinically useful and meaningful to patients and clinicians. They suggested that the prerequisites included a technological infrastructure capable of supporting data entry and joint decision-making in an accessible way, and a set of social conditions, including willingness from patients and clinicians alike to work together in new ways that build on the expertise of both parties. Follow-up interviews highlighted some of the obstacles, including technical challenges and practical constraints on refiguring relationships between clinicians and patients. CONCLUSIONS: The values and vision underlying the RCLS-CF were shared and clearly and consistently articulated by design stakeholders. The challenges to realization were often not at the level of principle, but were both practical and social in character. Lessons from this study may be useful to other systems looking to harness the power of "big data" registries, including patient-reported data, for care, research, and quality improvement.

Observational Study of Brain Atrophy and Cognitive Decline Comparing a Sample of Community-Dwelling People Taking Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Over Time.

BACKGROUND: Hypertension is an established risk factor for dementia. However, it is unclear whether there are differential effects of angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blockers (ARB) on brain health. In human observational studies, the evidence for superiority of either agent remains unclear. OBJECTIVE: To compare brain atrophy and cognitive decline between people treated with ACEi or ARB. METHODS: Participants aged 55-90 years without dementia had brain magnetic resonance imaging and neuropsychological assessments performed at 3 time points. The sample was enriched with people with type 2 diabetes (T2D). Multivariable mixed models were used to examine longitudinal associations of antihypertensive medication class with change in cognition and total brain volume. RESULTS: Of 565 people with longitudinal data, there were 163 on ACEi (mean age 69.9 years, T2D:64% with) and 125 on ARB (mean age 69.6 years, T2D:62%) at baseline. The baseline characteristics of those taking either an ACEi or ARB were similar with regards to age, sex, blood pressure control, and vascular risk factors. The mean duration of follow up was 3.2 years. The baseline association of ACEi and ARB use with total brain volume was similar in both groups. However, those taking an ARB had a slower rate of brain atrophy than those taking an ACEi (p = 0.031). Neither ACEi nor ARB use was associated with baseline cognitive function or cognitive decline. CONCLUSIONS: These results support the theory that ARB may be preferable to ACEi to reduce brain atrophy. The mechanisms underlying this differential association warrant further investigation.

How to be a very safe maternity unit: An ethnographic study.

Maternity care continues to be associated with avoidable harm that can result in serious disability and profound anguish for women, their children, and their families, and in high costs for healthcare systems. As in other areas of healthcare, improvement efforts have typically focused either on implementing and evaluating specific interventions, or on identifying the contextual features that may be generative of safety (e.g. structures, processes, behaviour, practices, and values), but the dialogue between these two approaches has remained limited. In this article, we report a positive deviance case study of a high-performing UK maternity unit to examine how it achieved and sustained excellent safety outcomes. Based on 143 h of ethnographic observations in the maternity unit, 12 semi-structured interviews, and two focus groups with staff, we identified six mechanisms that appeared to be important for safety: collective competence; insistence on technical proficiency; monitoring, coordination, and distributed cognition; clearly articulated and constantly reinforced standards of practice, behaviour, and ethics; monitoring multiple sources of intelligence about the unit's state of safety; and a highly intentional approach to safety and improvement. These mechanisms were nurtured and sustained through both a specific intervention (known as the PROMPT programme) and, importantly, the unit's contextual features: intervention and context shaped each other in both direct and indirect ways. The mechanisms were also influenced by the unit's structural conditions, such as staffing levels and physical environment. This study enhances understanding of what makes a maternity unit safe, paving the way for better design of improvement approaches. It also advances the debate on quality and safety improvement by offering a theoretically and empirically grounded analysis of the interplay between interventions and context of implementation.

Senior stakeholder views on policies to foster a culture of openness in the English National Health Service: a qualitative interview study.

OBJECTIVES: To examine the experiences of clinical and managerial leaders in the English healthcare system charged with implementing policy goals of openness, particularly in relation to improving employee voice. DESIGN: Semi-structured qualitative interviews. SETTING: National Health Service, regulatory and third-sector organisations in England. PARTICIPANTS: Fifty-one interviewees, including senior leaders in healthcare organisations (38) and policymakers and representatives of other relevant regulatory, legal and third-sector organisations (13). MAIN OUTCOME MEASURES: Not applicable. RESULTS: Participants recognised the limitations of treating the new policies as an exercise in procedural implementation alone and highlighted the need for additional 'cultural engineering' to engender change. However, formidable impediments included legacies of historical examples of detriment arising from speaking up, the anxiety arising from increased monitoring and the introduction of a legislative imperative and challenges in identifying areas characterised by a lack of openness and engaging with them to improve employee voice. Beyond healthcare organisations themselves, recent legal cases and examples of 'blacklisting' of whistle-blowers served to reinforce the view that giving voice to concerns was a risky endeavour. CONCLUSIONS: Implementation of procedural interventions to support openness is challenging but feasible; engineering cultural change is much more daunting, given deep-rooted and pervasive assumptions about what should be said and the consequences of mis-speaking, together with ongoing ambivalences in the organisational environment about the propriety of giving voice to concerns.

Fidelity or flexibility: An ethnographic study of the implementation and use of the Patient Activation Measure.

OBJECTIVE: To evaluate the use of the PAM in the English National Health service. The PAM is a validated scale that measures 'activation' (people's knowledge, skills, and confidence in managing their health) and assigns patients to four categories of activation (low-to-high). Some evidence suggests that higher activation levels correlate to better clinical outcomes and patient experiences, and lower healthcare costs. Empirical studies of implementing the PAM are scarce. METHODS: An ethnographic study of six healthcare organisations' PAM implementation focused on 'core-teams' who designed projects, and frontline staff and patients' experiences of those. Data comprised 123 hours of observation, 112 interviews, and document reviewing. Analysis used a constant-comparative approach. RESULTS: The PAM appealed as it fitted with different logics of measurement, offering a means of quantifying soft, process-oriented qualitative constructs used in tailoring care, whilst simultaneously producing reliable high-level outcome metrics. Data revealed challenges to these logics. The PAM's developers emphasised fidelity to ensure reliability but, in practice, flexibility was commonplace and often perceived as appropriate and beneficial by frontline staff. CONCLUSION: The intended logic of measurement is important in determining an appropriate balance of fidelity and flexibility and, therefore, reliability and patient benefit.

Towards a new paradigm in health research and practice? Collaborations for Leadership in Applied Health Research and Care.

PURPOSE: Collaborations for Leadership in Applied Health Research and Care (CLAHRCs) are a new UK initiative to promote collaboration between universities and healthcare organisations in carrying out and applying the findings of applied health research. But they face significant, institutionalised barriers to their success. This paper seeks to analyse these challenges and discuss prospects for overcoming them. DESIGN/METHODOLOGY/APPROACH: The paper draws on in-depth qualitative interview data from the first round of an ongoing evaluation of one CLAHRC to understand the views of different stakeholders on its progress so far, challenges faced, and emergent solutions. FINDINGS: The breadth of CLAHRCs' missions seems crucial to mobilise the diverse stakeholders needed to succeed, but also produces disagreement about what the prime goal of the Collaborations should be. A process of consensus building is necessary to instil a common vision among CLAHRC members, but deep-seated institutional divisions continue to orient them in divergent directions, which may need to be overcome through other means. ORIGINALITY/VALUE: This analysis suggests some of the key means by which those involved in joint enterprises such as CLAHRCs can achieve consensus and action towards a current goal, and offers recommendations for those involved in their design, commissioning and performance management.