Influenza vaccination and risk of stroke: self-controlled case-series study

Background: Stroke may be triggered by respiratory infections, including influenza. Influenza vaccination could therefore reduce risk of stroke. Previous studies of this association have shown conflicting results.We aimed to investigate whether influenza vaccination was associated with reduced risk of stroke. Methods: We used a self-controlled case series design. The General Practice Research Database (GPRD) was used to extract records of patients aged 18 years or over recorded with stroke (fatal or non-fatal) from September 2001 to May 2009. Statistical modelling with conditional Poisson regression was employed to compute incidence rate ratios (IRR). The incidence rate of stroke in fixed time periods after influenza vaccination was compared with the incidence rate during a baseline period. Results: There were 17,853 eligible individuals who received one or more influenza vaccinations and experienced a stroke during the observation period. The incidence of stroke was significantly reduced inthe first 59 days following influenza vaccination compared with the baseline period. We found reductionsof 55% (IRR 0.45; 95% CI 0.36–0.57) in the first 1–3 days after vaccination, 36% (0.64; 0.53–0.76) at 4–7days, 30% (0.70; 0.61–0.79) at 8–14 days, 24% (0.76; 0.70–0.84) at 15–28 days and 17% (0.83; 0.77–0.89)at 29–59 days after vaccination. Early vaccination between 1 September and 15 November showed a greater reduction in IRR compared to later vaccination given after mid-November. Conclusions: Influenza vaccination is associated with a reduction in incidence of stroke. This study sup-ports previous studies which have shown a beneficial association of influenza vaccination for stroke prevention

Influenza vaccination and pneumococcal vaccination and risk of stroke/TIA (IPVASTIA): matched case-control study using the General Practice Research Database

The problem Stroke is an important cause of death and long term illness worldwide. About 150 thousand people suffer a new or recurrent stroke each year in the United Kingdom and five percent of the population are affected. Many of those who have a stroke survive but suffer substantial disability and considerable social and economic distress. Strokes are more common in winter and after respiratory infections, such as influenza and pneumonia. This suggests that preventing respiratory infections might reduce the risk of stroke. There is insufficient and contradictory evidence for the effect of influenza and pneumococcal vaccination in preventing stroke/TIA. We aimed to investigate the association between influenza and pneumococcal vaccination with stroke/TIA. The approach We used a matched case-control design with data from the United Kingdom General Practice Research Database. Cases were aged at least 18 years at diagnosis of first stroke/TIA recorded between 01/09/2001 to 31/08/2009, with controls matched for sex, practice, age and calendar time. Data were analysed using conditional logistic regression, adjusted for vaccine risk groups, cardiovascular risk factors and drug treatments. We also adjusted further for comorbidities using the Charlson index and for functional capacity using frequency of GP consultations and home visits. Findings We included 94432 patients: 47216 cases and 47216 matched controls. A total of 21880 cases (46.3%) and 21383 controls (45.3%) had received influenza vaccination in the preceding season while 23306 cases (49.4%) and 21856 controls (46.3%) had received a pneumococcal vaccination at any time before the index date. Influenza vaccination within the same season was associated with a 13% reduction in risk of stroke in older people aged 65 years and above if the vaccine was administered early in the season (OR 0.87, 95% CI 0.83 to 0.91). Influenza vaccination in the same season as the index date was associated with a reduction in risk of stroke (adjusted odds ratio [OR] 0.90; 95% confidence interval [CI] 0.87 to 0.93); however, the reduction in risk of stroke was restricted to those aged over 65 years (adjusted OR 0.89, 95% CI 0.85 to 0.92) whereas there was no effect in those aged under 65 years (adjusted OR 0.92, 95% CI 0.83 to 1.01). Also we found that early influenza vaccination within the same season (1 September to 15 November) was associated with a significantly lower risk of stroke (adjusted OR 0.88; 95% CI 0.85 to 0.92) whereas this effect was absent with later vaccination (15 November to 31 January) (adjusted OR 1.04; 95% CI 0.97 to 1.11). The effect of influenza vaccination waned with time from vaccination with no significant effect beyond 3 months. After sensitivity analysis for unmeasured confounding there was no reduction in risk of stroke with pneumococcal vaccination. Consequences Early influenza vaccination in older people may confer additional benefits through reduction in stroke risk. This has important implications for the early administration of influenza vaccines. Pneumococcal vaccination within the previous five years was not associated with reduced odds of stroke/TIA. Our findings suggest that influenza vaccination may have additional benefits, over and above prevention of respiratory complications, in preventing stroke/TIA. Further experimental studies are needed

National survey of the injury prevention activities of children's centres

Children's centres were established across England to provide a range of services including early education, social care and health to pre-school children and their families. We surveyed children's centres to ascertain the activities they were undertaking to prevent unintentional injuries in the under fives. A postal questionnaire was sent to a sample of children's centre managers (n = 694). It included questions on current activities, knowledge and attitudes to injury prevention, health priorities and partnership working. Responses were received from 384 (56%) children's centres. Overall, 58% considered unintentional injury prevention to be one of the three main child health priorities for their centre. Over half the respondents (59%) did not know if there was an injury prevention group in their area, and 21% did not know if there was a home safety equipment scheme. Knowledge of how child injury deaths occur in the home was poor. Only 11% knew the major cause of injury deaths in children under five. Lack of both staff time and funding were seen as important barriers by children's centre staff to undertake injury prevention activities. Nearly all stated that training (97%) and assistance with planning injury prevention (94%) would be helpful to their centres. Children's centres need further support if they are to effectively tackle this important public health area

Cycling infrastructure for reducing cycling injuries in cyclists

© 2015 The Cochrane Collaboration. Background: Cycling is an attractive form of transport. It is beneficial to the individual as a form of physical activity that may fit more readily into an individual's daily routine, such as for cycling to work and to the shops, than other physical activities such as visiting a gym. Cycling is also beneficial to the wider community and the environment as a result of fewer motorised journeys. Cyclists are seen as vulnerable road users who are frequently in close proximity to larger and faster motorised vehicles. Cycling infrastructure aims to make cycling both more convenient and safer for cyclists. This review is needed to guide transport planning. Objectives: To: 1. evaluate the effects of different types of cycling infrastructure on reducing cycling injuries in cyclists, by type of infrastructure; 2. evaluate the effects of cycling infrastructure on reducing the severity of cycling injuries in cyclists; 3. evaluate the effects of cycling infrastructure on reducing cycling injuries in cyclists with respect to age, sex and social group. Search methods: We ran the most recent search on 2nd March 2015. We searched the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (OvidSP), Embase Classic + Embase(OvidSP), PubMed and 10 other databases. We searched websites, handsearched conference proceedings, screened reference lists of included studies and previously published reviews and contacted relevant organisations. Selection criteria: We included randomised controlled trials, cluster randomised controlled trials, controlled before-after studies, and interrupted time series studies which evaluated the effect of cycling infrastructure (such as cycle lanes, tracks or paths, speed management, roundabout design) on cyclist injury or collision rates. Studies had to include a comparator, that is, either no infrastructure or a different type of infrastructure. We excluded studies that assessed collisions that occurred as a result of competitive cycling. Data collection and analysis: Two review authors examined the titles and abstracts of papers obtained from searches to determine eligibility. Two review authors extracted data from the included trials and assessed the risk of bias. We carried out a meta-analysis using the random-effects model where at least three studies reported the same intervention and outcome. Where there were sufficient studies, as a secondary analysis we accounted for changes in cyclist exposure in the calculation of the rate ratios. We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach for the installation of cycle routes and networks. Main results: We identified 21 studies for inclusion in the review: 20 controlled before-after (CBA) studies and one interrupted time series (ITS) study. These evaluated a range of infrastructure including cycle lanes, advanced stop lines, use of colour, cycle tracks, cycle paths, management of the road network, speed management, cycle routes and networks, roundabout design and packages of measures. No studies reported medically-attended or self-reported injuries. There was no evidence that cycle lanes reduce the rate of cycle collisions (rate ratio 1.21, 95% CI 0.70 to 2.08). Taking into account cycle flow, there was no difference in collisions for cyclists using cycle routes and networks compared with cyclists not using cycle routes and networks (RR 0.40, 95% CI 0.15 to 1.05). There was statistically significant heterogeneity between the studies (I2 = 75%, Chi2 = 8.00 df = 2, P = 0.02) for the analysis adjusted for cycle flow. We judged the quality of the evidence regarding cycle routes and networks as very low and we are very uncertain about the estimate. These analyses are based on findings from CBA studies. From data presented narratively, the use of 20 mph speed restrictions in urban areas may be effective at reducing cyclist collisions. Redesigning specific parts of cycle routes that may be particularly busy or complex in terms of traffic movement may be beneficial to cyclists in terms of reducing the risk of collision. Generally, the conversion of intersections to roundabouts may increase the number of cycle collisions. In particular, the conversion of intersections to roundabouts with cycle lanes marked as part of the circulating carriageway increased cycle collisions. However, the conversion of intersections with and without signals to roundabouts with cycle paths may reduce the odds of collision. Both continuing a cycle lane across the mouth of a side road with a give way line onto the main road, and cycle tracks, may increase the risk of injury collisions in cyclists. However, these conclusions are uncertain, being based on a narrative review of findings from included studies. There is a lack of evidence that cycle paths or advanced stop lines either reduce or increase injury collisions in cyclists. There is also insufficient evidence to draw any robust conclusions concerning the effect of cycling infrastructure on cycling collisions in terms of severity of injury, sex, age, and level of social deprivation of the casualty. In terms of quality of the evidence, there was little matching of intervention and control sites. In many studies, the comparability of the control area to the intervention site was unclear and few studies provided information on other cycling infrastructures that may be in place in the control and intervention areas. The majority of studies analysed data routinely collected by organisations external to the study team, thus reducing the risk of bias in terms of systematic differences in assessing outcomes between the control and intervention groups. Some authors did not take regression-to-mean effects into account when examining changes in collisions. Longer data collection periods pre-and post-installation would allow for regression-to-mean effects and also seasonal and time trends in traffic volume to be observed. Few studies adjusted cycle collision rates for exposure. Authors' conclusions: Generally, there is a lack of high quality evidence to be able to draw firm conclusions as to the effect of cycling infrastructure on cycling collisions. There is a lack of rigorous evaluation of cycling infrastructure

Uptake, effectiveness and safety of COVID-19 vaccines in individuals at clinical risk due to immunosuppressive drug therapy or transplantation procedures: a population-based cohort study in England

: Background: Immunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understand and address the unique challenges faced by immunocompromised individuals in the context of COVID-19 vaccination. Methods: We analysed data from 12,274,946 people in the UK aged > 12 years from 01/12/2020 to 11/04/2022. Of these, 583,541 (4.8%) were immunocompromised due to immunosuppressive drugs, organ transplants, dialysis or chemotherapy. We undertook a cohort analysis to determine COVID-19 vaccine uptake, nested case–control analyses adjusted for comorbidities and sociodemographic characteristics to determine effectiveness of vaccination against COVID-19 hospitalisation, ICU admission and death, and a self-controlled case series assessing vaccine safety for pre-specified adverse events of interest. Results: Overall, 93.7% of immunocompromised individuals received at least one COVID-19 vaccine dose, with 80.4% having received three or more doses. Uptake reduced with increasing deprivation (hazard ratio [HR] 0.78 [95%CI 0.77–0.79] in the most deprived quintile compared to the least deprived quintile for the first dose). Estimated vaccine effectiveness against COVID-19 hospitalisation 2–6 weeks after the second and third doses compared to unvaccinated was 78% (95%CI 72–83) and 91% (95%CI 88–93) in the immunocompromised population, versus 85% (95%CI 83–86) and 86% (95%CI 85–89), respectively, for the general population. Results showed COVID-19 vaccines were protective against intensive care unit (ICU) admission and death in both populations, with effectiveness of over 92% against COVID-19-related death and up to 95% in reducing ICU admissions for both populations following the third dose. COVID-19 vaccines were generally safe for immunocompromised individuals, though specific doses of ChAdOx1, mRNA-1273 and BNT162b2 raised risks of specific cardiovascular/neurological conditions. Conclusions: COVID-19 vaccine uptake is high in immunocompromised individuals on immunosuppressive drug therapy or who have undergone transplantation procedures, with documented disparities by deprivation. Findings suggest that COVID-19 vaccines are protective against severe COVID-19 outcomes in this vulnerable population, and show a similar safety profile in immunocompromised individuals and the general population, despite some increased risk of adverse events. These results underscore the importance of ongoing vaccination prioritisation for this clinically at-risk population to maximise protection against severe COVID-19 outcomes

PHysical activity Implementation Study In Community-dwelling AduLts (PHISICAL): study protocol

Background: Falls in older people are a leading causes of unintentional injury. Due to an ageing population, injuries are likely to increase unless more is done to reduce older people’s falls risk. In clinical trials, the Falls Management Exercise (FaME) programme has reduced the rate of falls and falls-related injuries in community-dwelling older adults. However, the commissioning of FaME is inconsistent across England, potentially due to a lack of evidence that FaME can be delivered effectively in a ‘real world’ setting. The PHISICAL study is designed to study the implementation of FaME in a range of different settings in England. Methods: The PHISICAL study will use mixed-methods triangulation multi-level design to explore the implementation of FaME. Framework analysis of semi-structured interviews with up to 90 stakeholders (exercise programme users, service providers, referrers and commissioners) and observational data from locally-led communities of practice will identify the factors that influence FaME’s implementation. Quantitative, anonymised, routine service data from up to 650 exercise programme users, including measures of falls and physical activity, will allow assessment of whether the benefits of FaME reported in clinical trials translate to the ‘real world’ setting. Conclusion: The findings from this study will be used to develop a toolkit of resources and guidance to inform the commissioning and delivery of future FaME programmes. This study has the potential to inform public health prevention strategies, and in doing so may reduce the number of falls in the older population, whilst delivering cost savings to health and social care services

Common protocol for validation of the QCOVID algorithm across the four UK nations

Introduction The QCOVID algorithm is a risk prediction tool for infection and subsequent hospitalisation/death due to SARS-CoV-2. At the time of writing, it is being used in important policy-making decisions by the UK and devolved governments for combatting the COVID-19 pandemic, including deliberations on shielding and vaccine prioritisation. There are four statistical validations exercises currently planned for the QCOVID algorithm, using data pertaining to England, Northern Ireland, Scotland and Wales, respectively. This paper presents a common procedure for conducting and reporting on validation exercises for the QCOVID algorithm. Methods and analysis We will use open, retrospective cohort studies to assess the performance of the QCOVID risk prediction tool in each of the four UK nations. Linked datasets comprising of primary and secondary care records, virological testing data and death registrations will be assembled in trusted research environments in England, Scotland, Northern Ireland and Wales. We will seek to have population level coverage as far as possible within each nation. The following performance metrics will be calculated by strata: Harrell’s C, Brier Score, R2 and Royston’s D. Ethics and dissemination Approvals have been obtained from relevant ethics bodies in each UK nation. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journal

Dynamic updating of clinical survival prediction models in a changing environment

BackgroundOver time, the performance of clinical prediction models may deteriorate due to changes in clinical management, data quality, disease risk and/or patient mix. Such prediction models must be updated in order to remain useful. In this study, we investigate dynamic model updating of clinical survival prediction models. In contrast to discrete or one-time updating, dynamic updating refers to a repeated process for updating a prediction model with new data. We aim to extend previous research which focused largely on binary outcome prediction models by concentrating on time-to-event outcomes. We were motivated by the rapidly changing environment seen during the COVID-19 pandemic where mortality rates changed over time and new treatments and vaccines were introduced. MethodsWe illustrate three methods for dynamic model updating: Bayesian dynamic updating, recalibration, and full refitting. We use a simulation study to compare performance in a range of scenarios including changing mortality rates, predictors with low prevalence and the introduction of a new treatment. Next, the updating strategies were applied to a model for predicting 70-day COVID-19-related mortality using patient data from QResearch, an electronic health records database from general practices in the UK. ResultsIn simulated scenarios with mortality rates changing over time, all updating methods resulted in better calibration than not updating. Moreover, dynamic updating outperformed ad hoc updating. In the simulation scenario with a new predictor and a small updating dataset, Bayesian updating improved the C-index over not updating and refitting. In the motivating example with a rare outcome, no single updating method offered the best performance. ConclusionsWe found that a dynamic updating process outperformed one-time discrete updating in the simulations. Bayesian updating offered good performance overall, even in scenarios with new predictors and few events. Intercept recalibration was effective in scenarios with smaller sample size and changing baseline hazard. Refitting performance depended on sample size and produced abrupt changes in hazard ratio estimates between periods

Psychological morbidity and health related quality of life after injury: multicentre cohort study

Purpose To demonstrate the impact of psychological morbidity 1 month post-injury on subsequent post-injury quality of life (HRQoL) in a general injury population in the UK to inform development of trauma care and rehabilitation services. Methods Multicentre cohort study of 16–70-year-olds admitted to 4 UK hospitals following injury. Psychological morbidity and HRQoL (EQ-5D-3L) were measured at recruitment and 1, 2, 4 and 12 months post-injury. A reduction in EQ-5D compared to retrospectively assessed pre-injury levels of at least 0.074 was taken as the minimal important difference (MID). Multilevel logistic regression explored relationships between psychological morbidity 1 month post-injury and MID in HRQoL over the 12 months after injury. Results A total of 668 adults participated. Follow-up rates were 77% (1 month) and 63% (12 months). Substantial reductions in HRQoL were seen; 93% reported a MID at 1 month and 58% at 12 months. Problems with pain, mobility and usual activities were commonly reported at each time point. Depression and anxiety scores 1 month post-injury were independently associated with subsequent MID in HRQoL. The relationship between depression and HRQoL was partly explained by anxiety and to a lesser extent by pain and social functioning. The relationship between anxiety and HRQoL was not explained by factors measured in our study. Conclusions Hospitalised injuries result in substantial reductions in HRQoL up to 12 months later. Depression and anxiety early in the recovery period are independently associated with lower HRQoL. Identifying and managing these problems, ensuring adequate pain control and facilitating social functioning are key elements in improving HRQoL post-injury