Summary Background Concerns have been raised about the psychological effect of continued combat exposure and of repeated deployments. We examined the consequences of deployment to Iraq and ...Afghanistan on the mental health of UK armed forces from 2003 to 2009, the effect of multiple deployments, and time since return from deployment. Methods We reassessed the prevalence of probable mental disorders in participants of our previous study (2003–05). We also studied two new randomly chosen samples: those with recent deployment to Afghanistan, and those who had joined the UK armed forces since April, 2003, to ensure that the final sample continued to be representative of the UK armed forces. Between November, 2007, and September, 2009, participants completed a questionnaire about their deployment experiences and health outcomes. Findings 9990 (56%) participants completed the study questionnaire (8278 regulars, 1712 reservists). The prevalence of probable post-traumatic stress disorder was 4·0% (95% CI 3·5–4·5; n=376), 19·7% (18·7–20·6; n=1908) for symptoms of common mental disorders, and 13·0% (12·2–13·8; n=1323) for alcohol misuse. Deployment to Iraq or Afghanistan was significantly associated with alcohol misuse for regulars (odds ratio 1·22, 95% CI 1·02–1·46) and with probable post-traumatic stress disorder for reservists (2·83, 1·23–6·51). Regular personnel in combat roles were more likely than were those in support roles to report probable post-traumatic stress disorder (1·87, 1·26–2·78). There was no association with number of deployments for any outcome. There was some evidence for a small increase in the reporting of probable post-traumatic stress disorder with time since return from deployment in regulars (1·13, 1·03–1·24). Interpretation Symptoms of common mental disorders and alcohol misuse remain the most frequently reported mental disorders in UK armed forces personnel, whereas the prevalence of probable post-traumatic stress disorder was low. These findings show the importance of continued health surveillance of UK military personnel. Funding UK Ministry of Defence.
The use of electronic patient records for assessing outcomes in clinical trials is a methodological strategy intended to drive faster and more cost-efficient acquisition of results. The aim of this ...manuscript was to outline the data collection and management considerations of a maternity and perinatal clinical trial using data from electronic patient records, exemplifying the DESiGN Trial as a case study.
The DESiGN Trial is a cluster randomised control trial assessing the effect of a complex intervention versus standard care for identifying small for gestational age foetuses. Data on maternal/perinatal characteristics and outcomes including infants admitted to neonatal care, parameters from foetal ultrasound and details of hospital activity for health-economic evaluation were collected at two time points from four types of electronic patient records held in 22 different electronic record systems at the 13 research clusters. Data were pseudonymised on site using a bespoke Microsoft Excel macro and securely transferred to the central data store. Data quality checks were undertaken. Rules for data harmonisation of the raw data were developed and a data dictionary produced, along with rules and assumptions for data linkage of the datasets. The dictionary included descriptions of the rationale and assumptions for data harmonisation and quality checks.
Data were collected on 182,052 babies from 178,350 pregnancies in 165,397 unique women. Data availability and completeness varied across research sites; each of eight variables which were key to calculation of the primary outcome were completely missing in median 3 (range 1-4) clusters at the time of the first data download. This improved by the second data download following clarification of instructions to the research sites (each of the eight key variables were completely missing in median 1 (range 0-1) cluster at the second time point). Common data management challenges were harmonising a single variable from multiple sources and categorising free-text data, solutions were developed for this trial.
Conduct of clinical trials which use electronic patient records for the assessment of outcomes can be time and cost-effective but still requires appropriate time and resources to maximise data quality. A difficulty for pregnancy and perinatal research in the UK is the wide variety of different systems used to collect patient data across maternity units. In this manuscript, we describe how we managed this and provide a detailed data dictionary covering the harmonisation of variable names and values that will be helpful for other researchers working with these data.
Primary registry and trial identifying number: ISRCTN 67698474 . Registered on 02/11/16.
Monoclonal antibody (Mab) treatments have significantly improved the quality and quantity of life, but they are some of the most expensive treatments, resulting in a degree of hesitancy to introduce ...new Mab agents. A system for estimating the effect of Mab drugs, in general, would optimally inform health strategy and fully realize how a single scientific discovery can deliver health benefits. We evaluated such a method with several well-established Mab regimens.
We selected five different Mab regimens in oncology and rheumatology in England. We carried out two systematic literature reviews and meta-analyses to assess health outcomes (Health Assessment Questionnaire-Disability Index for rheumatoid arthritis; overall mortality for melanoma) from real-world data and compared them to the outcomes from randomized control trials (RCTs). We applied economic modeling to estimate the net monetary benefits for health outcomes for the estimated patient population size for each Mab regimen.
Meta-analyses of 27 eligible real-world data (RWD) sets and 26 randomized controlled trial (RCT) sets found close agreement between the observed and expected health outcomes. A Markov model showed the net positive monetary benefit in three Mab regimens and the negative benefit in two regimens. However, because of limited access to NHS data, the economic model made several assumptions about the number of treated patients and the cost of treatment to the NHS, the accuracy of which may affect the estimation of the net monetary benefit.
RCT results reliably inform the real-world experience of Mab treatments. Calculation of the net monetary benefit by the algorithm described provides a valuable overall measure of the health impact, subject to the accuracy of data inputs. This study provides a compelling case for building a comprehensive, systematized, and accessible database and related analytics, on all Mab treatments within health services.
The task repurposing of heterogeneous, distributed data for originally unintended research objectives is a non-trivial problem because the mappings required may not be precise. A particular case is ...clinical data collected for patient care being used for medical research. The fact that research repositories will record data differently means that assumptions must be made as how to transform of this data. Records of provenance that document how this process has taken place will enable users of the data warehouse to utilise the data appropriately and ensure that future data added from another source is transformed using comparable assumptions. For a provenance-based approach to be reusable and supportable with software tools, the provenance records must use a well-defined model of the transformation process. In this paper, we propose such a model, including a classification of the individual ‘sub-functions’ that make up the overall transformation. This model enables meaningful provenance data to be generated automatically. A case study is used to illustrate this approach and an initial classification of transformations that alter the information is created.
Objective
To evaluate the effectiveness of a brief supervised education, self‐management, and global upper extremity exercise training program, supplementing a home exercise regimen, for people with ...rheumatoid arthritis (RA; the Education, Self‐Management, and Upper Extremity Exercise Training in People with Rheumatoid Arthritis EXTRA program).
Methods
Adults with RA of ≤5 years' duration were randomized to receive either usual care or the EXTRA program comprising 4 (1‐hour) group education, self‐management, and global upper extremity exercise training sessions supplementing the first 2 weeks of a 12‐week individualized, functional home exercise regimen in addition to usual care. Outcome measures were assessed at baseline, 12 weeks (primary end point), and 36 weeks and included the Disabilities of the Arm, Shoulder, and Hand questionnaire (primary outcome measure), the Grip Ability Test, handgrip strength (N), the Arthritis Self‐Efficacy Scale (pain, function, and symptoms subscales), and the 28‐joint Disease Activity Score.
Results
One hundred eight participants (26 men, mean ± SD age 55 ± 15 years, mean ± SD disease duration 20 ± 19 months) were randomized to receive either usual care (n = 56) or the EXTRA program (n = 52). At 12 weeks, there was a significant between‐group difference in the mean change in disability (−6.8 95% confidence interval (95% CI) −12.6, −1.0; P = 0.022), function (−3.0 95% CI −5.0, −0.5; P = 0.011), nondominant handgrip strength (31.3N 95% CI 9.8, 52.8; P = 0.009), self‐efficacy (10.5 95% CI 1.6, 19.5; P = 0.021 for pain and 9.3 95% CI 0.5, 18.2; P = 0.039 for symptoms), and disease activity (−0.7 95% CI −1.4, 0.0; P = 0.047), all favoring the EXTRA program.
Conclusion
The EXTRA program improves upper extremity disability, function, handgrip strength, and self‐efficacy in people with RA, with no adverse effects on disease activity.
Abstract A-STAR is a prospective register of UK and Irish patients with atopic eczema receiving systemic immunomodulatory therapies. The register is designed to assess the short- and long-term ...clinical and cost-effectiveness and safety of such treatments in a real-world setting. We present descriptive data collected at cohort entry across 35 sites from 2018 to 13 December 2023, including patient demographics, comorbidities, past and current treatments, physician-assessed severity, patient outcomes and health resource utilization. In total 677 patients (mean age 28.9 years, SD 16.4, 44.6% female) have been recruited. Asthma, food allergies and allergic rhinoconjunctivitis were the most prevalent atopic comorbidities in the cohort (60.8%, 46.0% and 42.6%, respectively). Two-thirds (67.5%, n = 297) of patients were previously exposed to systemic treatment for atopic eczema, with on average to two (SD 1.4) systemic medications at baseline. When entering the register, patients had a mean Eczema Area and Severity Index of 20.0 (SD 12.7), Patient-Oriented Eczema Measure of 19.6 (SD 6.7), peak pruritus numerical rating scale of 6.8 (SD 2.2) and (Children’s) Dermatology Life Quality Index of 15.4 (SD 7.7). The most commonly started systemic medications at baseline were dupilumab (45.0%, n = 255), methotrexate (32.3%, n = 183) and ciclosporin (8.9%, n = 47), followed by upadacitinib (4.5%, n = 24), abrocitinib (3.5%, n = 20) and baricitinib (3.2%, n = 18). In total 44.3% (n = 297) of patients reported losing a median of 10 days (interquartile range 4–30) of usual activities due to atopic eczema in the 3 months prior to enrolment. Within 3 months before enrolment, 32% (n = 153) of patients had been treated in a day care unit, for a median of 2 days (interquartile range 1–2), while 7.7% (n = 37) had been hospitalized for their atopic eczema during the same period. As for EuroQol-5D at baseline, patients reported pain and anxiety or depression having a significant impact on their general health, with 84.7% and 68.8% of adults and 84% and 69.2% of children experiencing pain and anxiety or depression, respectively. Overall, 52.8% of adults and 59.6% of children reported atopic eczema having a negative impact on usual activities. A-STAR is a register of patients with atopic eczema receiving systemic immunomodulatory treatment. It collects data in different dimensions of treatment effectiveness, safety and health resource use. Further collection of health resource utilization data will help in devising an efficient strategy for accurate estimates for health economic modelling of atopic eczema systemic therapies. A-STAR is funded through BADERL, a registered not-for-profit company within the British Association of Dermatologists. BADERL receives income from AbbVie, Eli Lilly and Pfizer for providing pharmacovigilance services on their therapies. The A-STAR study protocol, study conduct and all decisions concerning data analyses, interpretation and publication are made independently of any industry involvement.
Abstract
As a visual-based specialty, dermatology has the opportunity to use artificial intelligence (AI) to aid diagnosis and guide precision management of skin diseases. To employ effective and ...safe AI, algorithms should be trained and validated on data sets that are representative of patient demographics in clinical practice. In our recent systematic review of AI image analysis studies in inflammatory skin conditions, ethnicity and Fitzpatrick skin type were reported in only four (6%) and 10 (16%) of 64 included studies, respectively. A systematic review of skin cancer image data sets similarly demonstrated poor ethnicity and Fitzpatrick skin type reporting, and under-representation of darker skin types (Wen D, Khan SM, Xu AJ et al. Characteristics of publicly available skin cancer image datasets: a systematic review. Lancet Digit Health 2022;4:e64–e74). Such bias in image acquisition limits the accuracy of AI tools when applied to real-world populations. We aimed to assess the representation of ethnic groups in our AI research and understand barriers to participation. We established a prospective observational cohort study in a national specialized psoriasis service based in South London, which seeks to develop AI algorithms for image-based assessment of psoriasis severity. Participants have photographs of their skin taken (both self-taken on participants’ own devices and professionally acquired in a studio) for AI image analysis. Images are securely stored in an ethically-approved research database in accordance with UK General Data Protection Regulations. Willingness to participate and reasons for declining were recorded. Of 557 patients approached between September 2021 and December 2022, 151 (27.1%) declined to participate in the AI study. The mean (SD) age of those willing and declining to participate was 47.4 (16.6) and 50.7 (16.2) years, respectively. Of those willing to participate, 57.5% were male vs. 53.6% who declined. Twenty-five per cent (n = 77/308) of individuals of white ethnicity declined to participate vs. 32% (n = 20/63) Indian/Pakistan/Bangladeshi, 33% (n = 6/18) black/black British, 50% (n = 5/10) Chinese/Japanese/Korean/Indochinese and 50% (1/2) of mixed ethnicity. Common reasons for declining participation included a disinclination to have photos taken, psoriasis affecting intimate sites, time constraints, medical reasons (e.g. poor mobility) and concerns regarding data security. Ninety-eight of 406 individuals who were willing to participate met the study-specific inclusion criteria (e.g. plaque psoriasis, Psoriasis Area and Severity Index > 3) and were recruited. Of those recruited, 82% (n = 80) were of white ethnicity, 9% (n = 9) Indian/Pakistan/Bangladeshi and 8% (n = 8) were black/black British. Seventeen (17%) had Fitzpatrick skin type V/VI. These data highlight ethnic inequalities in participation of AI image-analysis research. Further dissection of barriers to participation may inform strategies for ensuring more diverse and representative datasets, to maximize the potential of AI in healthcare.
BackgroundAntenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth ...Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care.Methods and findingsThis was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes.ConclusionsIn this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings.Trial registrationThis trial is registered with the ISRCTN registry, ISRCTN67698474.
Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. ...The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic.
To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence.
Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence.
Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49).
These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes.
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