The landscape of the methodology in drug repurposing using human genomic data: a systematic review.

The process of drug development is expensive and time-consuming. In contrast, drug repurposing can be introduced to clinical practice more quickly and at a reduced cost. Over the last decade, there has been a significant expansion of large biobanks that link genomic data to electronic health record data, public availability of various databases containing biological and clinical information and rapid development of novel methodologies and algorithms in integrating different sources of data. This review aims to provide a thorough summary of different strategies that utilize genomic data to seek drug-repositioning opportunities. We searched MEDLINE and EMBASE databases to identify eligible studies up until 1 May 2023, with a total of 102 studies finally included after two-step parallel screening. We summarized commonly used strategies for drug repurposing, including Mendelian randomization, multi-omic-based and network-based studies and illustrated each strategy with examples, as well as the data sources implemented. By leveraging existing knowledge and infrastructure to expedite the drug discovery process and reduce costs, drug repurposing potentially identifies new therapeutic uses for approved drugs in a more efficient and targeted manner. However, technical challenges when integrating different types of data and biased or incomplete understanding of drug interactions are important hindrances that cannot be disregarded in the pursuit of identifying novel therapeutic applications. This review offers an overview of drug repurposing methodologies, providing valuable insights and guiding future directions for advancing drug repurposing studies.

Appraising the Causal Role of Risk Factors in Coronary Artery Disease and Stroke: A Systematic Review of Mendelian Randomization Studies.

BACKGROUND Mendelian randomization (MR) offers a powerful approach to study potential causal associations between exposures and health outcomes by using genetic variants associated with an exposure as instrumental variables. In this systematic review, we aimed to summarize previous MR studies and to evaluate the evidence for causality for a broad range of exposures in relation to coronary artery disease and stroke. METHODS AND RESULTS MR studies investigating the association of any genetically predicted exposure with coronary artery disease or stroke were identified. Studies were classified into 4 categories built on the significance of the main MR analysis results and its concordance with sensitivity analyses, namely, robust, probable, suggestive, and insufficient. Studies reporting associations that did not perform any sensitivity analysis were classified as nonevaluable. We identified 2725 associations eligible for evaluation, examining 535 distinct exposures. Of them, 141 were classified as robust, 353 as probable, 110 as suggestive, and 926 had insufficient evidence. The most robust associations were observed for anthropometric traits, lipids, and lipoproteins and type 2 diabetes with coronary artery; disease and clinical measurements with coronary artery disease and stroke; and thrombotic factors with stroke. CONCLUSIONS Despite the large number of studies that have been conducted, only a limited number of associations were supported by robust evidence. Approximately half of the studies reporting associations presented an MR sensitivity analysis along with the main analysis that further supported the causality of associations. Future research should focus on more thorough assessments of sensitivity MR analyses and further assessments of mediation effects or nonlinearity of associations.

Dissecting the pathogenic effects of smoking and its hallmarks in blood DNA methylation on colorectal cancer risk.

BACKGROUND: Tobacco smoking is suggested as a risk factor for colorectal cancer (CRC), but the complex relationship and the potential pathway are not fully understood. METHODS: We performed two-sample Mendelian randomisation (MR) analyses with genetic instruments for smoking behaviours and related DNA methylation in blood and summary-level GWAS data of colorectal cancer to disentangle the relationship. Colocalization analyses and prospective gene-environment interaction analyses were also conducted as replication. RESULTS: Convincing evidence was identified for the pathogenic effect of smoking initiation on CRC risk and suggestive evidence was observed for the protective effect of smoking cessation in the univariable MR analyses. Multivariable MR analysis revealed that these associations were independent of other smoking phenotypes and alcohol drinking. Genetically predicted methylation at CpG site cg17823346 [ZMIZ1] were identified to decrease CRC risk; while genetically predicted methylation at cg02149899 would increase CRC risk. Colocalization and gene-environment interaction analyses added further evidence to the relationship between epigenetic modification at cg17823346 [ZMIZ1] as well as cg02149899 and CRC risk. DISCUSSION: Our study confirms the significant association between tobacco smoking, DNA methylation and CRC risk and yields a novel insight into the pathogenic effect of tobacco smoking on CRC risk.

Development and Validation of Risk Prediction Models for Colorectal Cancer in Patients with Symptoms.

We aimed to develop and validate prediction models incorporating demographics, clinical features, and a weighted genetic risk score (wGRS) for individual prediction of colorectal cancer (CRC) risk in patients with gastroenterological symptoms. Prediction models were developed with internal validation [CRC Cases: n = 1686/Controls: n = 963]. Candidate predictors included age, sex, BMI, wGRS, family history, and symptoms (changes in bowel habits, rectal bleeding, weight loss, anaemia, abdominal pain). The baseline model included all the non-genetic predictors. Models A (baseline model + wGRS) and B (baseline model) were developed based on LASSO regression to select predictors. Models C (baseline model + wGRS) and D (baseline model) were built using all variables. Models' calibration and discrimination were evaluated through the Hosmer-Lemeshow test (calibration curves were plotted) and C-statistics (corrected based on 1000 bootstrapping). The models' prediction performance was: model A (corrected C-statistic = 0.765); model B (corrected C-statistic = 0.753); model C (corrected C-statistic = 0.764); and model D (corrected C-statistic = 0.752). Models A and C, that integrated wGRS with demographic and clinical predictors, had a statistically significant improved prediction performance. Our findings suggest that future application of genetic predictors holds significant promise, which could enhance CRC risk prediction. Therefore, further investigation through model external validation and clinical impact is merited.

Exploring the cross-cancer effect of smoking and its fingerprints in blood DNA methylation on multiple cancers: A Mendelian randomization study.

Aberrant smoking-related DNA methylation has been widely investigated as a carcinogenesis mechanism, but whether the cross-cancer epigenetic pathways exist remains unclear. We conducted two-sample Mendelian randomization (MR) analyses respectively on smoking behaviors (age of smoking initiation, smoking initiation, smoking cessation, and lifetime smoking index [LSI]) and smoking-related DNA methylation to investigate their effect on 15 site-specific cancers, based on a genome-wide association study (GWAS) of 1.2 million European individuals and an epigenome-WAS (EWAS) of 5907 blood samples of Europeans for smoking and 15 GWASs of European ancestry for multiple site-specific cancers. Significantly identified CpG sites were further used for colocalization analysis, and those with cross-cancer effect were validated by overlapping with tissue-specific eQTLs. In the genomic MR, smoking measurements of smoking initiation, smoking cessation and LSI were suggested to be casually associated with risk of seven types of site-specific cancers, among which cancers at lung, cervix and colorectum were provided with strong evidence. In the epigenetic MR, methylation at 75 CpG sites were reported to be significantly associated with increased risks of multiple cancers. Eight out of 75 CpG sites were observed with cross-cancer effect, among which cg06639488 (EFNA1), cg12101586 (CYP1A1) and cg14142171 (HLA-L) were validated by eQTLs at specific cancer sites, and cg07932199 (ATXN2) had strong evidence to be associated with cancers of lung (coefficient, 0.65, 95% confidence interval [CI], 0.31-1.00), colorectum (0.90 [0.61, 1.18]), breast (0.31 [0.20, 0.43]) and endometrium (0.98 [0.68, 1.27]). These findings highlight the potential practices targeting DNA methylation-involved cross-cancer pathways.

Reproductive history differs by molecular subtypes of breast cancer among women aged ≤ 50 years in Scotland diagnosed 2009-2016: a cross-sectional study.

BACKGROUND: The aetiology of breast cancers diagnosed ≤ 50 years of age remains unclear. We aimed to compare reproductive risk factors between molecular subtypes of breast cancer, thereby suggesting possible aetiologic clues, using routinely collected cancer registry and maternity data in Scotland. METHODS: We conducted a cross-sectional study of 4108 women aged ≤ 50 years with primary breast cancer diagnosed between 2009 and 2016 linked to maternity data. Molecular subtypes of breast cancer were defined using immunohistochemistry (IHC) tumour markers, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and tumour grade. Age-adjusted polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of number of births, age at first birth and time since last birth with IHC-defined breast cancer subtypes. Luminal A-like was the reference compared to luminal B-like (HER2-), luminal B-like (HER2+), HER2-overexpressed and triple-negative breast cancer (TNBC). RESULTS: Mean (SD) for number of births, age at first birth and time since last birth was 1.4 (1.2) births, 27.2 (6.1) years and 11.0 (6.8) years, respectively. Luminal A-like was the most common subtype (40%), while HER2-overexpressed and TNBC represented 5% and 15% of cases, respectively. Larger numbers of births were recorded among women with HER2-overexpressed and TNBC compared with luminal A-like tumours (> 3 vs 0 births, OR 1.87, 95%CI 1.18-2.96; OR 1.44, 95%CI 1.07-1.94, respectively). Women with their most recent birth > 10 years compared to < 2 years were less likely to have TNBC tumours compared to luminal A-like (OR 0.63, 95%CI 0.41-0.97). We found limited evidence for differences by subtype with age at first birth. CONCLUSION: Number of births and time since last birth differed by molecular subtypes of breast cancer among women aged ≤ 50 years. Analyses using linked routine electronic medical records by molecularly defined tumour pathology data can be used to investigate the aetiology and prognosis of cancer.

Breast cancer incidence and survival in Scotland by socio-economic deprivation and tumour subtype.

BACKGROUND: Women from socio-economically deprived areas are less likely to develop and then to survive breast cancer (BC). Whether associations between deprivation and BC incidence and survival differ by tumour molecular subtypes and mode of detection in Scotland are unknown. METHODS: Data consisted of 62,378 women diagnosed with invasive BC between 2000 and 2016 in Scotland. Incidence rates and time trends were calculated for oestrogen receptor positive (ER+) and negative (ER-) tumours and stratified by the Scottish Index of Multiple Deprivation (SIMD) quintiles and screening status. SIMD is an area-based measure derived across seven domains: income, employment, education, health, access to services, crime and housing. We calculated adjusted hazard ratios (aHR [95% confidence intervals]) for BC death by immunohistochemical surrogates of molecular subtypes for the most versus the least deprived quintile. We adjusted for mode of detection and other confounders. RESULTS: In Scotland, screen-detected ER+tumour incidence increased over time, particularly in the least deprived quintile [Average Annual Percentage Change (AAPC) = 2.9% with 95% CI from 1.2 to 4.7]. No marked differences were observed for non-screen-detected ER+tumours or ER- tumours by deprivation. BC mortality was higher in the most compared to the least deprived quintile irrespective of ER status (aHR = 1.29 [1.18, 1.41] for ER+ and 1.27 [1.09, 1.47] for ER- tumours). However, deprivation was associated with significantly higher mortality for luminal A and HER2-enriched tumours (aHR = 1.46 [1.13, 1.88] and 2.10 [1.23, 3.59] respectively) but weaker associations for luminal B and TNBC tumours that were not statistically significant. CONCLUSIONS: Deprivation is associated with differential BC incidence trends for screen-detected ER+tumours and with higher mortality for select tumour subtypes. Future efforts should evaluate factors that might be associated with reduced survival in deprived populations and monitor progress stratified by tumour subtypes and mode of detection.

Effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality: systematic review and meta-analysis.

OBJECTIVE: To review the evidence on the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, CINAHL, Biosis, Joanna Briggs, Global Health, and World Health Organization COVID-19 database (preprints). ELIGIBILITY CRITERIA FOR STUDY SELECTION: Observational and interventional studies that assessed the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality. MAIN OUTCOME MEASURES: The main outcome measure was incidence of covid-19. Secondary outcomes included SARS-CoV-2 transmission and covid-19 mortality. DATA SYNTHESIS: DerSimonian Laird random effects meta-analysis was performed to investigate the effect of mask wearing, handwashing, and physical distancing measures on incidence of covid-19. Pooled effect estimates with corresponding 95% confidence intervals were computed, and heterogeneity among studies was assessed using Cochran's Q test and the I2 metrics, with two tailed P values. RESULTS: 72 studies met the inclusion criteria, of which 35 evaluated individual public health measures and 37 assessed multiple public health measures as a "package of interventions." Eight of 35 studies were included in the meta-analysis, which indicated a reduction in incidence of covid-19 associated with handwashing (relative risk 0.47, 95% confidence interval 0.19 to 1.12, I2=12%), mask wearing (0.47, 0.29 to 0.75, I2=84%), and physical distancing (0.75, 0.59 to 0.95, I2=87%). Owing to heterogeneity of the studies, meta-analysis was not possible for the outcomes of quarantine and isolation, universal lockdowns, and closures of borders, schools, and workplaces. The effects of these interventions were synthesised descriptively. CONCLUSIONS: This systematic review and meta-analysis suggests that several personal protective and social measures, including handwashing, mask wearing, and physical distancing are associated with reductions in the incidence covid-19. Public health efforts to implement public health measures should consider community health and sociocultural needs, and future research is needed to better understand the effectiveness of public health measures in the context of covid-19 vaccination. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178692.

Distinct temporal trends in breast cancer incidence from 1997 to 2016 by molecular subtypes: a population-based study of Scottish cancer registry data.

BACKGROUND: We describe temporal trends in breast cancer incidence by molecular subtypes in Scotland because public health prevention programmes, diagnostic and therapeutic services are shaped by differences in tumour biology. METHODS: Population-based cancer registry data on 72,217 women diagnosed with incident primary breast cancer from 1997 to 2016 were analysed. Age-standardised rates (ASR) and age-specific incidence were estimated by tumour subtype after imputing the 8% of missing oestrogen receptor (ER) status. Joinpoint regression and age-period-cohort models were used to assess whether significant differences were observed in incidence trends by ER status. RESULTS: Overall, ER-positive tumour incidence increased by 0.4%/year (95% confidence interval (CI): -0.1, 1.0). Among routinely screened women aged 50-69 years, we observed an increase in ASR from 1997 to 2011 (1.6%/year, 95% CI: 1.2-2.1). ER-negative tumour incidence decreased among all ages by 2.5%/year (95% CI: -3.9 to -1.1%) over the study period. Compared with the 1941-1959 birth cohort, women born in 1912-1940 had lower incidence rate ratios (IRR) for ER+ tumours and women born in 1960-1986 had lower IRR for ER- tumours. CONCLUSIONS: Future incidence and survival reporting should be monitored by molecular subtypes to inform clinical planning and cancer control programmes.

Follow-up care after treatment for prostate cancer: evaluation of a supported self-management and remote surveillance programme.

BACKGROUND: Alternative models of cancer follow-up care are needed to ameliorate pressure on services and better meet survivors' long-term needs. This paper reports an evaluation of a service improvement initiative for the follow-up care of prostate cancer patients based on remote monitoring and supported self-management. METHODS: This multi-centred, historically controlled study compared patient reported outcomes of men experiencing the new Programme with men experiencing a traditional clinic appointment model of follow-up care, who were recruited in the period immediately prior to the introduction of the Programme. Data were collected by self-completed questionnaires, with follow up measurement at four and eight months post-baseline. The primary outcome was men's unmet survivorship needs, measured by the Cancer Survivors' Unmet Needs Survey. Secondary outcomes included cancer specific quality of life, psychological wellbeing and satisfaction with care. The analysis was intention to treat. Regression analyses were conducted for outcomes at each time point separately, controlling for pre-defined clinical and demographic variables. All outcome analyses are presented in the paper. Costs were compared between the two groups. RESULTS: Six hundred and twenty-seven men (61%) were consented to take part in the study (293 in the Programme and 334 in the comparator group.) Regarding the primary measure of unmet survivorship needs, 25 of 26 comparisons favoured the Programme, of which 4 were statistically significant. For the secondary measures of activation for self-management, quality of life, psychological well-being and lifestyle, 20 of 32 comparisons favoured the Programme and 3 were statistically significant. There were 22 items on the satisfaction with care questionnaire and 13 were statistically significant. Per participant costs (British pounds, 2015) in the 8 month follow up period were slightly lower in the programme than in the comparator group (£289 versus £327). The Programme was acceptable to patients. CONCLUSION: The Programme is shown to be broadly comparable to traditional follow-up care in all respects, adding to evidence of the viability of such models.

Compassionate care intervention for hospital nursing teams caring for older people: a pilot cluster randomised controlled trial.

OBJECTIVE: Compassionate care continues to be a focus for national and international attention, but the existing evidence base lacks the experimental methodology necessary to guide the selection of effective interventions for practice. This study aimed to evaluate the Creating Learning Environments for Compassionate Care (CLECC) intervention in improving compassionate care. SETTING: Ward nursing teams (clusters) in two English National Health Service hospitals randomised to intervention (n=4) or control (n=2). Intervention wards comprised two medicines for older people (MOPs) wards and two medical/surgical wards. Control wards were both MOPs. PARTICIPANTS: Data collected from 627 patients and 178 staff. EXCLUSION CRITERIA: reverse barrier nursed, critically ill, palliative or non-English speaking. All other patients and all nursing staff and Health Care Assistant HCAs were invited to participant, agency and bank staff were excluded. INTERVENTION: CLECC, a workplace intervention focused on developing sustainable leadership and work-team practices to support the delivery of compassionate care. CONTROL: No educational activity. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary-Quality of Interaction Schedule (QuIS) for observed staff-patient interactions. Secondary-patient-reported evaluations of emotional care in hospital (PEECH); nurse-reported empathy (Jefferson Scale of Empathy). RESULTS: Trial proceeded as per protocol, randomisation was acceptable. Some but not all blinding strategies were successful. QuIS observations achieved 93% recruitment rate with 25% of patient sample cognitively impaired. At follow-up there were more total positive (78% vs 74%) and less total negative (8% vs 11%) QuIS ratings for intervention wards versus control wards. Sixty-three per cent of intervention ward patients scored lowest (ie, more negative) scores on PEECH connection subscale, versus 79% of control. This was not a statistically significant difference. No statistically significant differences in nursing empathy were observed. CONCLUSIONS: Use of experimental methods is feasible. The use of structured observation of staff-patient interaction quality is a promising outcome measure inclusive of hard to reach groups. TRIAL REGISTRATION NUMBER: ISRCTN16789770.

Follow-up care after treatment for prostate cancer: protocol for an evaluation of a nurse-led supported self-management and remote surveillance programme.

BACKGROUND: As more men survive a diagnosis of prostate cancer, alternative models of follow-up care that address men's enduring unmet needs and are economical to deliver are needed. This paper describes the protocol for an ongoing evaluation of a nurse-led supported self-management and remote surveillance programme implemented within the secondary care setting. METHODS/DESIGN: The evaluation is taking place within a real clinical setting, comparing the outcomes of men enrolled in the Programme with the outcomes of a pre-service change cohort of men, using a repeated measures design. Men are followed up at four and 8 months post recruitment on a number of outcomes, including quality of life, unmet need, psychological wellbeing and activation for self-management. An embedded health economic analysis and qualitative evaluation of implementation processes are being undertaken. DISCUSSION: The evaluation will provide important information regarding the effectiveness, cost effectiveness and implementation of an integrated supported self-management follow-up care pathway within secondary care.

Reliability, feasibility, and validity of the quality of interactions schedule (QuIS) in acute hospital care: an observational study.

BACKGROUND: Research into relational care in hospitals will be facilitated by a focus on staff-patient interactions. The Quality of Interactions Schedule (QuIS) uses independent observers to measure the number of staff-patient interactions within a healthcare context, and to rate these interactions as 'positive social'; 'positive care'; 'neutral'; 'negative protective'; or 'negative restrictive'. QuIS was developed as a research instrument in long term care settings and has since been used for quality improvement in acute care. Prior to this study, its use had not been standardised, and reliability and validity in acute care had not been established. METHODS: In 2014 and 2015 a three - phase study was undertaken to develop and test protocols for the use of QuIS across three acute wards within one NHS trust in England. The phases were: (1) A pilot of 16 h observation which developed implementation strategies for QuIS in this context; (2) training two observers and undertaking 16 h of paired observation to inform the development of training protocols; (3) training four nurses and two lay volunteers according to a finalised protocol followed by 36 h of paired observations to test inter-rater agreement. Additionally, patients were asked to rate interactions and to complete a shortened version of the Patient Evaluation of Emotional Care during Hospitalisation (PEECH) questionnaire. RESULTS: Protocols were developed for the use of QuIS in acute care. Patients experienced an average of 6.7 interactions/patient/h (n = 447 interactions). There was close agreement between observers in relation to the number of interactions observed (Intraclass correlation coefficient (ICC) = 0.97) and moderate to substantial agreement on the quality of interactions (absolute agreement 73%, kappa 0.53 to 0.62 depending on weighting scheme). There was 79% agreement (weighted kappa 0.40: P < 0.001; indicating fair agreement) between patients and observers over whether interactions were positive, negative or neutral. CONCLUSIONS: Observers using clear QuIS protocols can achieve levels of agreement that are acceptable for the use of QuIS as a research instrument. There is fair agreement between observers and patients' rating of interactions. Further research is needed to explore the relationship between QuIS measures and reported patient experience.

Inter-rater reliability of the QuIS as an assessment of the quality of staff-inpatient interactions.

BACKGROUND: Recent studies of the quality of in-hospital care have used the Quality of Interaction Schedule (QuIS) to rate interactions observed between staff and inpatients in a variety of ward conditions. The QuIS was developed and evaluated in nursing and residential care. We set out to develop methodology for summarising information from inter-rater reliability studies of the QuIS in the acute hospital setting. METHODS: Staff-inpatient interactions were rated by trained staff observing care delivered during two-hour observation periods. Anticipating the possibility of the quality of care varying depending on ward conditions, we selected wards and times of day to reflect the variety of daytime care delivered to patients. We estimated inter-rater reliability using weighted kappa, κ w , combined over observation periods to produce an overall, summary estimate, [Formula: see text]. Weighting schemes putting different emphasis on the severity of misclassification between QuIS categories were compared, as were different methods of combining observation period specific estimates. RESULTS: Estimated [Formula: see text] did not vary greatly depending on the weighting scheme employed, but we found simple averaging of estimates across observation periods to produce a higher value of inter-rater reliability due to over-weighting observation periods with fewest interactions. CONCLUSIONS: We recommend that researchers evaluating the inter-rater reliability of the QuIS by observing staff-inpatient interactions during observation periods representing the variety of ward conditions in which care takes place, should summarise inter-rater reliability by κ w , weighted according to our scheme A4. Observation period specific estimates should be combined into an overall, single summary statistic [Formula: see text], using a random effects approach, with [Formula: see text], to be interpreted as the mean of the distribution of κ w across the variety of ward conditions. We draw attention to issues in the analysis and interpretation of inter-rater reliability studies incorporating distinct phases of data collection that may generalise more widely.

Quantity and quality of interaction between staff and older patients in UK hospital wards: A descriptive study.

BACKGROUND: The quality of staff-patient interactions underpins the overall quality of patient experience and can affect other important outcomes. However no studies have been identified that comprehensively explore both the quality and quantity of interactions in general hospital settings. AIMS & OBJECTIVES: To quantify and characterise the quality of staff-patient interactions and to identify factors associated with negative interaction ratings. SETTING: Data were gathered at two acute English NHS hospitals between March and April 2015. Six wards for adult patients participated including medicine for older people (n=4), urology (n=1) and orthopaedics (n=1). METHODS: Eligible patients on participating wards were randomly selected for observation. Staff-patient interactions were observed using the Quality of Interactions Schedule. 120h of care were observed with each 2h observation session determined from a balanced random schedule (Monday-Friday, 08:00-22:00h). Multilevel logistic regression models were used to determine factors associated with negative interactions. RESULTS: 1554 interactions involving 133 patients were observed. The median length of interaction was 36s with a mean of 6 interactions per patient per hour. Seventy three percent of interactions were categorized as positive, 17% neutral and 10% negative. Forty percent of patients had at least one negative interaction (95% confidence interval 32% to 49%). Interactions initiated by the patient (adjusted Odds Ratio [OR] 5.30), one way communication (adjusted OR 10.70), involving two or more staff (adjusted OR 5.86 for 2 staff, 6.46 for 3+ staff), having a higher total number of interactions (adjusted OR 1.09 per unit increase), and specific types of interaction content were associated with increased odds of negative interaction (p<0.05). In the full multivariable model there was no significant association with staff characteristics, skill mix or staffing levels. Patient agitation at the outset of interaction was associated with increased odds of negative interaction in a reduced model. There was no significant association with gender, age or cognitive impairment. There was substantially more variation at ward level (variance component 1.76) and observation session level (3.49) than at patient level (0.09). CONCLUSION: These findings present a unique insight into the quality and quantity of staff-patient interactions in acute care. While a high proportion of interactions were positive, findings indicate that there is scope for improvement. Future research should focus on further exploring factors associated with negative interactions, such as workload and ward culture.