Acceptability of virtual psychiatric consultations for routine follow-ups post COVID-19 pandemic for people with intellectual disabilities: cross-sectional study.

BACKGROUND: After the rapid implementation of digital health services during the COVID-19 pandemic, a paucity of research exists about the suitability of remote consulting in people with intellectual disabilities and their carers, particularly for neuropsychiatric reviews. AIM: This study examines when remote neuropsychiatric routine consulting is suitable for this population. METHOD: A survey was conducted of people with intellectual disabilities and their carers, examining their preference between face-to-face and video consultations for ongoing neuropsychiatric reviews within a rural countywide intellectual disability service in Cornwall, England (population: 538 000). The survey was sent to all adults with intellectual disabilities open to the service on 30 July 2022, closing on 30 September 2022. Participants were asked to provide responses on 11 items predesigned and co-produced between clinicians and experts by experience. The entire service caseload of people had White ethnicity, reflecting the ethnic demographics of Cornwall. Responses received without consent were excluded from the study dataset. RESULTS: Of 271 eligible participants, 119 responses were received, 104 of whom consented to having their anonymised data used for research analysis. There were no significant differences between preferences and age and gender variables. There was no statistically significant difference regarding preference for the reintroduction of face-to-face appointments (52.0%) compared with video consultations (48.0%). Travel distance (>10 miles) to the clinical setting was important but did not outweigh benefits for those preferring a face-to-face appointment. CONCLUSIONS: This study offers insights into the factors that influence preferences about what type of neuropsychiatric appointment is most suitable for people with intellectual disabilities.

Investigating the impact of undiagnosed anxiety and depression on health and social care costs and quality of life: cross-sectional study using household health survey data.

BACKGROUND: There is uncertainty around the costs and health impacts of undiagnosed mental health problems. AIMS: Using survey data, we aim to understand the costs and health-related quality-of-life decrements from undiagnosed anxiety/depression. METHOD: We analysed survey data from two waves of the North West Coast Household Health Survey, which included questions on disease, medications, and Patient Health Questionnaire 9 (PHQ-9) and Generalised Anxiety Disorder 7 (GAD-7) scores (depression and anxiety scales). People were judged as having undiagnosed anxiety/depression problems if they scored ≥5 on the PHQ-9 or GAD-7, and did not declare a mental health issue or antidepressant prescription. Linear regression for EuroQol 5-Dimension 3-Level (EQ-5D-3L) index scores, and Tweedie regression for health and social care costs, were used to estimate the impact of undiagnosed mental health problems, controlling for age, gender, deprivation and other health conditions. RESULTS: Around 26.5% of participants had undiagnosed anxiety/depression. The presence of undiagnosed anxiety/depression was associated with reduced EQ-5D-3L index scores (0.040 lower on average) and increased costs (£250 ($310) per year on average). Using a higher cut-off score of 10 on the PHQ-9 and GAD-7 for undiagnosed anxiety/depression had similar increased costs but a greater reduction in EQ-5D-3L index scores (0.076 on average), indicating a larger impact on health-related quality of life. CONCLUSIONS: Having undiagnosed anxiety or depression increases costs and reduces health-related quality of life. Reducing stigma and increasing access to cost-effective treatments will have population health benefits.

Characteristics of mental health stability during COVID-19: An online survey with people residing in a city region of the North West of England.

BACKGROUND AND AIM: Despite the significant mental health challenges the COVID-19 pandemic and its associated government measures have presented, research has shown that the majority of people have adapted and coped well. The aim of this study was i) to determine the proportion of people with mental stability and volatility during the pandemic in a North West England city region sample and ii) to establish group differences in psychosocial variables. Mental stability and volatility refer to the extent to which individuals reported change in levels of common mental health symptoms over the course of 12 weeks. No change in mental health over the 12 weeks reflected mental stability whilst change in mental health reflected mental volatility. METHOD: A two-wave-online survey (N = 163) was used to explore the psychological and social impact of the pandemic on relatively disadvantaged neighbourhoods within the region. The data collected represents 12 weeks of individual pandemic experience between mid-June and mid-December 2020. A three-level composite common mental health change variable was created combining self-reported anxiety and depression to group stable, volatile, and very volatile individuals in terms of the changeability of their mental health. Kruskal-Wallis with post-hoc tests were used to determine how people with mental stability and volatility differed on factors categorised within an ecological framework of resilience (individual, community, societal, and COVID-19 specific). RESULTS: Individuals categorised as 'stable' in terms of mental health symptoms (63.6%) had better mental and physical health; were more tolerant of uncertainty; and reported higher levels of resilience and wellbeing compared to 'very volatile' people (19.8%). These individuals also reported feeling less socially isolated, experienced a greater sense of belonging to their community which was more likely to fulfil their needs, and were more likely to have access to green space nearby for their recommended daily exercise. 'Stable' individuals did not report worrying any more during the pandemic than usual and tolerated uncertainty better compared to those in the 'volatile' group. IMPLICATIONS: The majority of participants in this sample were mentally stable and coping well with the challenges presented by the pandemic. The resilience of these individuals was related to key place-based factors such as a strong sense of community and useable local assets. The data showcase the role of place-based social determinants in supporting resilience and thereby highlight key preventative measures for public mental health during times of international crisis.

Socioeconomic and health factors related to polypharmacy and medication management: analysis of a Household Health Survey in North West Coast England.

OBJECTIVES: To examine the socioeconomic and demographic drivers associated with polypharmacy (5-9 medicines), extreme polypharmacy (9-20 medicines) and increased medication count. DESIGN, SETTING AND PARTICIPANTS: A total of 5509 participants, from two waves of the English North West Coast, Household Health Survey were analysed OUTCOME MEASURES: Logistic regression modelling was used to find associations with polypharmacy and extreme polypharmacy. A negative binomial regression identified associations with increased medication count. Descriptive statistics explored associations with medication management. RESULTS: Age and number of health conditions account for the greatest odds of polypharmacy. ORs (95% CI) were greatest for those aged 65+ (3.87, 2.45 to 6.13) and for those with ≥5 health conditions (10.87, 5.94 to 19.88). Smaller odds were seen, for example, in those prescribed cardiovascular medications (3.08, 2.36 to 4.03), or reporting >3 emergency attendances (1.97, 1.23 to 3.17). Extreme polypharmacy was associated with living in a deprived neighbourhood (1.54, 1.06 to 2.26). The greatest risk of increased medication count was associated with age, number of health conditions and use of primary care services. Relative risks (95% CI) were greatest for those aged 65+ (2.51, 2.23 to 2.82), those with ≥5 conditions (10.26, 8.86 to 11.88) or those reporting >18 primary care visits (2.53, 2.18 to 2.93). Smaller risks were seen in, for example, respondents with higher levels of income deprivation (1.35, 1.03 to 1.77). Polypharmic respondents were more likely to report medication management difficulties associated with taking more than one medicine at a time (p<0.001). Furthermore, individuals reporting a mental health condition, were significantly more likely to consistently report difficulties managing their medication (p<0.001). CONCLUSION: Age and number of health conditions are most associated with polypharmacy. Thus, delaying or preventing the onset of long-term conditions may help to reduce polypharmacy. Interventions to reduce income inequalities and health inequalities generally could support a reduction in polypharmacy, however, more research is needed in this area. Furthermore, increased prevention and support, particularly with medication management, for those with mental health conditions may reduce adverse medication effects.

The impact of an integrated care intervention on mortality and unplanned hospital admissions in a disadvantaged community in England: A difference-in-differences study.

BACKGROUND: Many health systems are experimenting with integrated care models to improve outcomes and reduce healthcare demand. Evidence for effects on health service utilisation is variable, with few studies investigating impacts on mortality or differences by socioeconomic group. OBJECTIVE: To examine the impact of a multidisciplinary, integrated care team intervention on emergency admissions and mortality, and whether effects differed by deprivation group. DESIGN: A longitudinal matched controlled study using difference-in-differences analysis comparing the change in unplanned emergency admissions twelve months before and after the intervention, and inverse probability of treatment-weighted survival analysis comparing mortality, between intervention and matched control groups. SETTING: A relatively deprived city in England, U.K. INTERVENTION: A case-management integrated care programme delivered through multidisciplinary teams and aimed at complex needs and/or high hospitalisation risk patients. RESULTS: The intervention was associated with a small increase in emergency admissions of 15 per 1,000 patients per month (95% CI 5 to 24, p = 0.003) after the intervention relative to the control group and no significant change in survival between intervention and control groups (HR 0.9, 95% CI 0.84 to 1.13, p = 0.7). Effects were similar across age and deprivation groups. CONCLUSIONS: It is unlikely that similar interventions lead to reduced emergency admissions or increased survival. Further studies should use experimental methods and assess impacts on quality of life.

Factors Affecting Patient and Physician Engagement in Remote Health Care for Heart Failure: Systematic Review.

BACKGROUND: Adult chronic heart failure mainly affects an elderly population with multiple comorbidities that often require frequent medical visits to prevent poor health outcomes. However, the heart failure disease process reduces their independence by reducing mobility, exercise tolerance, and cognitive decline. Remote care technologies can bridge the gap in care for these patients by allowing them to be followed up within the comfort of their home and encourage their self-care. However, patients, carers, and health care professionals need to engage with the technology for it to be useful. OBJECTIVE: This systematic review explores qualitative primary studies of remote care technologies used in heart failure, to determine the factors that affect user engagement with the technology. This is explored from the perspective of patients, carers, and health care professionals. METHODS: Relevant studies published between January 1, 1990, and September 19, 2020, were identified from EMBASE, Ovid MEDLINE, PubMed, Cochrane Library, and Scopus. These studies were then synthesized using thematic analysis. Relevant user experiences with remote care were extracted using line-by-line coding. These codes were summarized into secondary codes and core concepts, which were further merged into overarching themes that encapsulate user experience with remote care. RESULTS: The review included 47 studies, which led to the generation of 5 overarching themes that affect engagement: (1) "Convenience" relates to time saved by the intervention; (2) "Clinical Care" relates to perceived quality of care and health outcomes; (3) "Communication" involves feedback and interaction between patients, staff, and carers; (4) "Education" concerns the tailored information provided; and (5) "Ease of Use" relates to accessibility and technical barriers to engagement. Each theme was applied to each user base of patient, carer, and health care professional in a different manner. CONCLUSIONS: The 5 themes identified highlight aspects of remote care that facilitate engagement, and should be considered in both future design and trials evaluating these technologies.

Low vitamin D levels do not predict risk of autoimmune disease following alemtuzumab treatment for multiple sclerosis.

Alemtuzumab is a highly effective treatment for multiple sclerosis (MS) and the treatment strategy of two cycles 12 months apart has a lot of appeal to patients. Widespread use of alemtuzumab has been tempered by treatment emergent autoimmunity which is seen in approximately one-third of patients in the 5 years after treatment. It has been postulated that relative vitamin D deficiency may be a causative factor in this setting. We have conducted a retrospective case-control study looking at the association of vitamin D and other potentially relevant clinical factors on the likelihood of treatment emergent autoimmune disease following alemtuzumab. Occurrence of autoimmunity was monitored for clinically and through the Bloodwatch® monitoring program. Clinical data and vitamin D levels obtained as part of routine clinical practice were recorded. Vitamin D levels were seasonally adjusted. Only cases with complete data were included. Univariable and multivariable Cox proportional hazards analyses were performed. There were 113 patients treated with alemtuzumab for whom there was complete data. Median follow up was 4.4 years. Risk of autoimmune disease was not associated with lower vitamin D levels. Risk of autoimmune disease was associated with female sex (HR 3.5) and with higher EDSS score at treatment. The association with EDSS was lost when analysis was restricted to those with 4 or more years of follow up. These data do not support a role for vitamin D supplementation in the prevention of autoimmune disease following alemtuzumab. Males have a lower risk of autoimmunity following alemtuzumab.

Examining the uptake of predictive BRCA testing in the UK; findings and implications.

Predictive BRCA testing is offered to asymptomatic individuals to predict future risk where a variant has been identified in a relative. It is uncertain whether all eligible relatives access testing, and whether this is related to health care inequalities. Our aim was to analyse trends and inequalities in uptake of testing, and identify predictors of testing and time-to-receipt of testing. A database from April 2010 to March 2017 was collated. Multivariate analysis explored individual associations with testing. Predictor variables included gender, BRCA test type, cancer history, Index of Multiple Deprivation (IMD) and education status. To evaluate factors associated with time-to-testing, a Cox proportional-hazards (CP) model was used. Of 779 tests undertaken, 336 (43.1%) were identified with a BRCA variant. A total of 537 (68.9%) were female and in 83.4% (387/464) of probands, predictive testing was received by relatives. Analysis identified inequalities since decreased testing was found when the proband was unaffected by cancer (OR 0.14, 95% CI 0.06-0.33). Median time-to-testing was 390 days (range, 0-7090 days) and the CP model also identified inequalities in the hazard ratio (HR) for testing for people aged >40 was higher than for aged <40 (HR 1.41, 95% CI 1.20-1.67) and BRCA2 testing was higher than for BRCA1 testing (HR 1.39, 95% CI 1.18-1.64). Reduced testing was found when probands were unaffected by cancer and time-to-testing was found to vary by age and BRCA1/2 test. Given limited study sample size, further research is recommended to examine inequalities in predictive BRCA testing.

The longitudinal NIHR ARC North West Coast Household Health Survey: exploring health inequalities in disadvantaged communities.

BACKGROUND: The Household Health Survey (HHS) was developed to understand the socioeconomic determinants of mental and physical health, and health inequalities in health and social care. This paper aims to provide a detailed rationale of the development and implementation of the survey and explore socio-economic variations in physical and mental health and health care. METHODS: This comprehensive longitudinal public health survey was designed and piloted in a disadvantaged area of England, comprising questions on housing, physical health, mental health, lifestyle, social issues, environment, work, and finances. After piloting, the HHS was implemented across 28 neighbourhoods - 10 disadvantaged neighbourhoods for learning (NfLs), 10 disadvantaged comparator sites, and eight relatively advantaged areas, in 2015 and 2018. Participants were recruited via random sampling of households in pre-selected neighbourhoods based on their areas of deprivation. RESULTS: 7731 residents participated in Wave 1 (N = 4319) and 2 (n = 3412) of the survey, with 871 residents having participated in both. Mental health, physical health, employment, and housing quality were poorer in disadvantaged neighbourhoods than in relatively advantaged areas. CONCLUSIONS: This survey provides important insights into socio-economic variations in physical and mental health, with findings having implications for improved care provision to enable residents from any geographical or socio-economic background to access suitable care.

Has the introduction of direct oral anticoagulants (DOACs) in England increased emergency admissions for bleeding conditions? A longitudinal ecological study.

OBJECTIVE: There is concern about long-term safety of direct oral coagulants (DOACs) in clinical practice. Our aim was to investigate whether the introduction of DOACs compared with vitamin-K antagonists in England was associated with a change in admissions for bleeding or thromboembolic complications. SETTING: 5508 General practitioner (GP) practices in England between 2011 and 2016. PARTICIPANTS: All GP practices in England with a registered population size of greater than 1000 that had data for all 6 years. MAIN OUTCOME MEASURE: The rate of emergency admissions to hospital for bleeding or thromboembolism, per 100 000 population for each GP practice in England. MAIN EXPOSURE MEASURE: The annual number of DOAC items prescribed for each GP practice population as a proportion of all anticoagulant items prescribed. DESIGN: This longitudinal ecological study used panel regression models to investigate the association between trends in DOAC prescribing within GP practice populations and trends in emergency admission rates for bleeding and thromboembolic conditions, while controlling for confounders. RESULTS: For each additional 10% of DOACs prescribed as a proportion of all anticoagulants, there was a 0.9% increase in bleeding complications (rate ratio 1.008 95% CI 1.003 to 1.013). The introduction of DOACs between 2011 and 2016 was associated with additional 4929 (95% CI 2489 to 7370) emergency admissions for bleeding complications. Increased DOAC prescribing was associated with a slight decline in admission for thromboembolic conditions. CONCLUSION: Our data show that the rapid increase in prescribing of DOACs after changes in National Institute for Health and Care Excellence guidelines in 2014 may have been associated with a higher rate of emergency admissions for bleeding conditions. These consequences need to be considered in assessing the benefits and costs of the widespread use of DOACs.

Impact of community-based chronic obstructive pulmonary disease service, a multidisciplinary intervention in an area of high deprivation: a longitudinal matched controlled study.

OBJECTIVE: To examine the effects of a consultant-led, community-based chronic obstructive pulmonary disease (COPD) service, based in a highly deprived area on emergency hospital admissions. DESIGN: A longitudinal matched controlled study using difference-in-differences analysis to compare the change in outcomes in the intervention population to a matched comparison population, 5 years before and after implementation. SETTING: A deprived district in the North West of England between 2005 and 2016. INTERVENTION: A community-based, consultant-led COPD service providing diagnostics, treatment and rehabilitation from 2011 to 2016. MAIN OUTCOME MEASURES: Emergency hospital admissions, length of stay per emergency admission and emergency readmissions for COPD. RESULTS: The intervention was associated with 24 fewer emergency COPD admissions per 100 000 population per year (95% CI -10.6 to 58.8, p=0.17) in the postintervention period, relative to the control group. There were significantly fewer emergency admissions in populations with medium levels of deprivation (64 per 100 000 per year; 95% CI 1.8 to 126.9) and among men (60 per 100 000 per year; 95% CI 12.3 to 107.3). CONCLUSION: We found limited evidence that the service reduced emergency hospital admissions, after an initial decline the effect was not sustained. The service, however, may have been more effective in some subgroups.

Impact of a community-based cardiovascular disease service intervention in a highly deprived area.

OBJECTIVE: To examine the effects on emergency hospital admissions, length of stay and emergency re-admissions of providing a consultant-led, community-based cardiovascular diagnostic, treatment and rehabilitation service, based in a highly deprived area in the North West of England. METHODS: A longitudinal matched controlled study using difference-in-differences analysis compared the change in outcomes in the intervention population, to the change in outcomes in a matched comparison population that had not received the intervention, 5 years before and after implementation. The outcomes were emergency hospitalisations, length of inpatient stay and re-admission rates for cardiovascular disease (CVD). RESULTS: Findings show that the intervention was associated with 66 fewer emergency CVD admissions per 100 000 population per year (95% CI 22.13 to 108.98) in the post-intervention period, relative to the control group. No significant measurable effects on length of stay or emergency re-admission rates were observed. CONCLUSION: This consultant-led, community-based cardiovascular diagnostic, treatment and rehabilitation service was associated with a lower rate of emergency hospital admissions in a highly disadvantaged population. Similar approaches could be an effective component of strategies to reduce unplanned hospital admissions.

Public involvement in the dissemination of the North West Coast Household Health Survey: Experiences and lessons of co-producing research together.

BACKGROUND: Engaging with the public is a key element of health research; however, little work has examined experiences of public involvement in research dissemination. The aim of this paper was to assess the extent of public involvement, experiences of public advisers and resulting changes in the dissemination of the North West Coast Household Health Survey (HHS). METHODS: Three writing groups allowed public advisers to contribute to the dissemination of the HHS. A public workshop was set up to aid the co-production of the research evidence and discuss the experiences of public advisers involved with the survey in March 2018. A focus group with public advisers was conducted in August 2018 to understand their experiences of involvement. Data were analysed using thematic analysis and coded by two researchers. Writing groups are still on-going. RESULTS: Fourteen public advisers contributed via three face-to-face writing groups, by actively interpreting findings and helping in the write-up of research articles and by presenting talks at the public workshop. At the workshop, seven public advisors contributed to setting priorities for data analysis from the HHS. Five public advisers took part in the focus group, which highlighted that whilst public advisers were generally satisfied with their involvement, they would like to be involved in more activities. CONCLUSIONS: Members of the public shaped the dissemination of evidence and provided guidance for future steps. Public advisers were mostly positive about their involvement in the dissemination of the HHS, but highlighted the need for more transparency and support from researchers.

Trends in BRCA testing and socioeconomic deprivation.

BRCA testing received much publicity following Angelina Jolie's editorial "My Medical Choice" in May 2013 and updated NICE clinical guidance (CG164) in June 2013. We assessed the effect of these two concurrent events on BRCA testing in one UK catchment area and relate this to socioeconomic deprivation. A database of 1393 patients who received BRCA testing was collated. This included individuals with breast/ovarian cancer, and those unaffected by cancer, where a relative has a ≥10% probability of carrying a BRCA variant which affects function. A segmented regression was conducted to estimate changes in testing. To examine the relative distribution of testing by deprivation, the deprivation status of patients who received testing was examined. Between April 2010 and March 2017, testing increased 11-fold and there was an 84% increase (P = 0.006) in BRCA1/2 testing in the month following both publications. In the pre-publication period, there was no statistically significant difference in testing between advantaged and disadvantaged areas (OR 1.21, 95% CI 0.99-1.48; P = 0.06). In the post-publication period helped by a larger sample size, the difference was statistically significant (OR 1.18, 95% CI 1.08-1.29; P = 0.0002) and of a similar magnitude to the pre-publication period. Testing increased following Jolie's editorial and NICE guidance update. However, further research is needed to examine differences in testing by the deprivation group which adjusts for confounders.

Implementation of genotype-guided dosing of warfarin with point-of-care genetic testing in three UK clinics: a matched cohort study.

BACKGROUND: Warfarin is a widely used oral anticoagulant. Determining the correct dose required to maintain the international normalised ratio (INR) within a therapeutic range can be challenging. In a previous trial, we showed that a dosing algorithm incorporating point-of-care genotyping information ('POCT-GGD' approach) led to improved anticoagulation control. To determine whether this approach could translate into clinical practice, we undertook an implementation project using a matched cohort design. METHODS: At three clinics (implementation group; n = 119), initial doses were calculated using the POCT-GGD approach; at another three matched clinics (control group; n = 93), patients were dosed according to the clinic's routine practice. We also utilised data on 640 patients obtained from routinely collected data at comparable clinics. Primary outcome was percentage time in target INR range. Patients and staff from the implementation group also provided questionnaire feedback on POCT-GGD. RESULTS: Mean percentage time in INR target range was 55.25% in the control group and 62.74% in the implementation group; therefore, 7.49% (95% CI 3.41-11.57%) higher in the implementation group (p = 0.0004). Overall, patients and staff viewed POCT-GGD positively, suggesting minor adjustments to allow smooth implementation into practice. CONCLUSIONS: In the first demonstration of the implementation of genotype-guided dosing, we show that warfarin dosing determined using an algorithm incorporating genetic and clinical factors can be implemented smoothly into clinic, to ensure target INR range is reached sooner and maintained. The findings are like our previous randomised controlled trial, providing an alternative method for improving the risk-benefit of warfarin use in daily practice.

What are the social predictors of accident and emergency attendance in disadvantaged neighbourhoods? Results from a cross-sectional household health survey in the north west of England.

OBJECTIVES: The aim of this study was to identify the most important determinants of accident and emergency (A&E) attendance in disadvantaged areas. DESIGN, SETTING AND PARTICIPANTS: A total of 3510 residents from 20 disadvantaged neighbourhoods in the North West Coast area in England completed a comprehensive public health survey. MAIN OUTCOME MEASURES: Participants were asked to complete general background information, as well as information about their physical health, mental health, lifestyle, social issues, housing and environment, work and finances, and healthcare service usage. Only one resident per household could take part in the survey. Poisson regression analysis was employed to assess the predictors of A&E attendance frequency in the previous 12 months. RESULTS: 31.6% of the sample reported having attended A&E in the previous 12 months, ranging from 1 to 95 visits. Controlling for demographic and health factors, not being in employment and living in poor quality housing increased the likelihood of attending an A&E service. Service access was also found to be predictive of A&E attendance insofar as there were an additional 18 fewer A&E attendances per 100 population for each kilometre closer a person lived to a general practitioner (GP) practice, and 3 fewer attendances per 100 population for each kilometre further a person lived from an A&E department. CONCLUSIONS: This is one of the first surveys to explore a comprehensive set of socio-economic factors as well as proximity to both GP and A&E services as predictors of A&E attendance in disadvantaged areas. Findings from this study suggest the need to address both socioeconomic issues, such as employment and housing quality, as well as structural issues, such as public transport and access to primary care, to reduce the current burden on A&E departments.

Trastuzumab uptake in HER2-positive breast cancer patients: a systematic review and meta-analysis of observational studies.

Overexpression of the HER2 gene is predictive of treatment benefit with trastuzumab therapy for breast cancer (BC) patients. The study objective was to investigate whether all eligible patients with HER2-positive BC initiated trastuzumab therapy. A systematic search was conducted through PubMed, Web of Science PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Library. From 2651 studies identified, 107 observational studies were included for full text review, of which 26 met the inclusion criteria and an additional 7 studies were identified through citation searching. Two independent reviewers extracted data for accuracy and completeness. From 33 observational studies, 14,644 patients were exposed to trastuzumab therapy. Age range varied across studies; the youngest cohort had a median age of 50 and the oldest had a median age of 84. Sample sizes ranged from 11 to 1928 and included patients from 10 countries. Studies were heterogenous and few studies accounted for confounders. We identified large variability in uptake of trastuzumab in HER2-positive early BC patients (9.1-100%) and metastatic BC patients (50.8-84.0%). The pooled uptake was 71.3% (95% CI 64.6-77.9%), with high heterogeneity (I2 = 99.05%). The most conservative predictors of higher uptake included younger age (OR 2.09; 95% CI 1.36-3.20) and lower Charlson Comorbidity Index of patients (OR 1.62; 95% CI 1.32-1.99). In addition, tumour characteristics including higher tumour grade (OR 1.73; 95% CI 1.23-2.45), larger tumour size (OR 1.80; 95% CI 1.54-2.10), advanced tumour stage (OR 2.07; 95% CI 1.44-2.96) and hormone receptor negative tumor (OR 1.54; 95% CI 1.35-1.77) were associated with higher uptake. The uptake of trastuzumab therapy varied widely between studies and across subgroups suggesting that there may be some inequalities in the use of this agent. However, our findings should be interpreted with caution due to study heterogeneity and potential confounding, and thus additional studies of individual level data which control for confounders are needed to understand more about inequalities in uptake.

The development of morphological representations in young readers: a cross-modal priming study.

The way children organize words in their memory has intrigued many researchers in the past 20 years. Given the large number of morphologically complex words in many languages, the influence of morphemes on this organization is being increasingly examined. The aim of this study was to understand how morphemic information influences English-speaking children's word recognition. Children in grades 3 and 5 were asked to complete a lexical decision priming task. Prime-target pairs varied in semantic similarity, with low (e.g., belly-bell), moderate (e.g., lately-late), and high similarity relations (e.g., boldly-bold). There were also word pairs similar in form only (e.g., spinach-spin) and in semantics only (e.g., garbage-trash). Primes were auditory and targets were presented visually. Analyses of children's lexical decision times revealed graded priming effects as a function of the convergence of form and meaning. These results indicate that developing readers do not necessarily need to lexicalize morphological units to facilitate word recognition. Their ability to process the morphological structure of words depends on their ability to develop connections between form and meaning.