Use of healthcare services before diagnosis of attention-deficit/hyperactivity disorder: a population-based matched case-control study.

OBJECTIVE: To compare use of healthcare services and reasons for attendance by children and young people (CYP) with attention-deficit/hyperactivity disorder (ADHD) versus non-ADHD controls. DESIGN: Population-based matched case-control study. SETTING: English primary care electronic health records with linked hospital records from the Clinical Practice Research Datalink, 1998-2015. PARTICIPANTS: 8127 CYP with an ADHD diagnosis aged 4-17 years at the time of diagnosis and 40 136 non-ADHD controls matched by age, sex and general practitioner (GP) practice. MAIN OUTCOME MEASURES: Medical diagnoses, prescriptions, hospital admissions and hospital procedures in the 2 years before diagnosis (or the index date for controls). RESULTS: CYP with ADHD attended healthcare services twice as often as controls (rate ratios: GP: 2.0, 95% CI=2.0, 2.1; hospital 1.8, 95% CI=1.8, 1.9). CYP with ADHD attended their GP, received prescriptions and were admitted to hospital for a wide range of reasons. The strongest association for GP attendances, comparing CYP with versus without ADHD, was for 'mental and behavioural disorders' (OR=25.2, 95% CI=23.3, 27.2). Common reasons for GP attendance included eye, ear, nose, throat, oral (OR=1.5, 95% CI=1.4, 1.5) and conditions such as asthma (OR=1.3, 95% CI=1.3, 1.4) or eczema (OR=1.2, 95% CI=1.0, 1.3). CONCLUSIONS: Two years before diagnosis, CYP with ADHD attended healthcare services twice as often as CYP without. CYP with ADHD had increased rates of physical conditions, such as asthma and eczema. These contacts may be an opportunity for earlier recognition and diagnosis of ADHD.

A systems approach to the safety and efficiency of prescribing at the primary-secondary care interface.

The interface between primary and secondary care represents a highly complex and heterogeneous system that continues to pose risks to the safety and quality of care. Many issues relate to prescribing activities, and suboptimal information sharing between stakeholders can lead to avoidable harm events and system inefficiencies that increase workload. The framework of a systems approach is used to structure four key interface issues: medicines reconciliation, prescribing at secondary care outpatient appointments, shared records, and quality of communication. We outline opportunities for improved safety and efficiency, and identify key barriers that need to be addressed. Significant further development is required for the measures discussed. We recommend the use of a systems approach to methodologically support this process, particularly due to the inherent system-wide understanding of problems that it generates. We argue such understanding is essential to ensure that risks and workload are not shifted around a system, without overall gain.

How can communication to GPs at hospital discharge be improved? A systems approach.

BACKGROUND: Poor communication to GPs at hospital discharge threatens patient safety and continuity of care, with reliance on discharge summaries that are commonly written by the most junior doctors. Previous quality improvement efforts have largely focused on adherence to standardised templates, with limited success. A lack of understanding has been identified as a cause of the issue's resistance to decades of improvement work. AIM: To understand the system of communication to GPs at hospital discharge, with a view to identifying potential routes to improvement. DESIGN & SETTING: A qualitative exploration of the secondary-to-primary care communication system surrounding a large UK hospital. METHOD: A systems approach, recently defined for the healthcare domain, was used to structure and thematically analyse interviews (n = 18) of clinical and administrative staff from both sides of the primary-secondary care interface, and a subsequent focus group. RESULTS: The largely one-way communication system structure and the low level of hospital stakeholder insight into recipient GP needs emerged as consistent hindrances to system performance. More open lines of communication and shared records might enable greater collaboration to share feedback and resolve informational deficits. Teaching sessions and assessments for medical students and junior doctors led by GPs could help to instil the importance of detail and nuance when using standardised communication templates. CONCLUSION: Facilitating the sharing of performance insights between stakeholder groups emerged as the key theme of how communication might be improved. The empirical measures proposed have the potential to mitigate the safety risks of key barriers to performance such as patient complexity.

Systems approach to health service design, delivery and improvement: a systematic review and meta-analysis.

OBJECTIVES: To systematically review the evidence base for a systems approach to healthcare design, delivery or improvement. DESIGN: Systematic review with meta-analyses. METHODS: Included were studies in any patients, in any healthcare setting where a systems approach was compared with usual care which reported quantitative results for any outcomes for both groups. We searched Medline, Embase, HMIC, Health Business Elite, Web of Science, Scopus, PsycINFO and CINAHL from inception to 28 May 2019 for relevant studies. These were screened, and data extracted independently and in duplicate. Study outcomes were stratified by study design and whether they reported patient and/or service outcomes. Meta-analysis was conducted with Revman software V.5.3 using ORs-heterogeneity was assessed using I2 statistics. RESULTS: Of 11 405 records 35 studies were included, of which 28 (80%) were before-and-after design only, five were both before-and-after and concurrent design, and two were randomised controlled trials (RCTs). There was heterogeneity of interventions and wide variation in reported outcome types. Almost all results showed health improvement where systems approaches were used. Study quality varied widely. Exploratory meta-analysis of these suggested favourable effects on both patient outcomes (n=14, OR=0.52 (95% CI 0.38 to 0.71) I2=91%), and service outcomes (n=18, OR=0.40 (95% CI 0.31 to 0.52) I2=97%). CONCLUSIONS: This study suggests that a systems approaches to healthcare design and delivery results in a statistically significant improvement to both patient and service outcomes. However, better quality studies, particularly RCTs are needed.PROSPERO registration numberCRD42017065920.

Efficacy of RNA polymerase II inhibitors in targeting dormant leukaemia cells.

BACKGROUND: Dormant cells are characterised by low RNA synthesis. In contrast, cancer cells can be addicted to high RNA synthesis, including synthesis of survival molecules. We hypothesised that dormant cancer cells, already low in RNA, might be sensitive to apoptosis induced by RNA Polymerase II (RP2) inhibitors that further reduce RNA synthesis. METHODS: We cultured leukaemia cells continuously in vitro in the presence of an mTOR inhibitor to model dormancy. Apoptosis, damage, RNA content and reducing capacity were evaluated. We treated dormancy-enriched cells for 48 hours with the nucleoside analogues ara-C, 5-azacytidine and clofarabine, the topoisomerase targeting agents daunorubicin, etoposide and irinotecan and three multikinase inhibitors with activity against RP2 - flavopiridol, roscovitine and TG02, and we measured growth inhibition and apoptosis. We describe use of the parameter 2 × IC50 to measure residual cell targeting. RNA synthesis was measured with 5-ethynyl uridine. Drug-induced apoptosis was measured flow cytometrically in primary cells from patients with acute myeloid leukaemia using a CD34/CD71/annexinV gating strategy to identify dormant apoptotic cells. RESULTS: Culture of the KG1a cell line continuously in the presence of an mTOR inhibitor induced features of dormancy including low RNA content, low metabolism and low basal ROS formation in the absence of a DNA damage response or apoptosis. All agents were more effective against the unmanipulated than the dormancy-enriched cells, emphasising the chemoresistant nature of dormant cells. However, the percentage of cell reduction by RP2 inhibitors at 2 × IC50 was significantly greater than that of other agents. RP2 inhibitors strongly inhibited RNA synthesis compared with other drugs. We also showed that RP2 inhibitors induce apoptosis in proliferating and dormancy-enriched KG1a cells and in the CD71neg CD34pos subset of primary acute myeloid leukaemia cells. CONCLUSION: We suggest that RP2 inhibitors may be a useful class of agent for targeting dormant leukaemia cells.