OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide and methotrexate monitoring, and factors associated with change in monitoring rate.

AIMS: The COVID-19 pandemic created unprecedented pressure on healthcare services. This study investigates whether disease-modifying antirheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic. METHODS: A population-based cohort study was conducted using the OpenSAFELY platform to access electronic health record data from 24.2 million patients registered at general practices using TPP's SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations. RESULTS: An acute increase in the rate of missed monitoring occurred across the study population (+12.4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70-79 year-olds: +13.7 percentage points; females: +12.8 percentage points), regions (North West: +17.0 percentage points), medications (leflunomide: +20.7 percentage points) and monitoring tests (blood pressure: +24.5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Consistent differences were observed in overall missed monitoring rates between several groups throughout the study. CONCLUSION: DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions and patient groups highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should evaluate the causes of the differences identified between groups.

OpenSAFELY: A platform for analysing electronic health records designed for reproducible research.

Electronic health records (EHRs) and other administrative health data are increasingly used in research to generate evidence on the effectiveness, safety, and utilisation of medical products and services, and to inform public health guidance and policy. Reproducibility is a fundamental step for research credibility and promotes trust in evidence generated from EHRs. At present, ensuring research using EHRs is reproducible can be challenging for researchers. Research software platforms can provide technical solutions to enhance the reproducibility of research conducted using EHRs. In response to the COVID-19 pandemic, we developed the secure, transparent, analytic open-source software platform OpenSAFELY designed with reproducible research in mind. OpenSAFELY mitigates common barriers to reproducible research by: standardising key workflows around data preparation; removing barriers to code-sharing in secure analysis environments; enforcing public sharing of programming code and codelists; ensuring the same computational environment is used everywhere; integrating new and existing tools that encourage and enable the use of reproducible working practices; and providing an audit trail for all code that is run against the real data to increase transparency. This paper describes OpenSAFELY's reproducibility-by-design approach in detail.

The impact of COVID-19 on the cancer care of adolescents and young adults and their well-being: Results from an online survey conducted in the early stages of the pandemic.

BACKGROUND: Because of the global spread of coronavirus disease 2019 (COVID-19), oncology departments across the world have rapidly adapted their cancer care protocols to balance the risk of delaying cancer treatments and the risk of COVID-19 exposure. COVID-19 and associated changes may have an impact on the psychosocial functioning of patients with cancer and survivors. This study was designed to determine the impact of the COVID-19 pandemic on young people living with and beyond cancer. METHODS: In this cross-sectional study, 177 individuals, aged 18 to 39 years, were surveyed about the impact of COVID-19 on their cancer care and psychological well-being. Participants also reported their information needs with respect to COVID-19. Responses were summarized with a content analysis approach. RESULTS: This was the first study to examine the psychological functioning of young patients and survivors during the first weeks of the COVID-19 pandemic. A third of the respondents reported increased levels of psychological distress, and as many as 60% reported feeling more anxious than they did before COVID-19. More than half also wanted more information tailored to them as young patients with cancer. CONCLUSIONS: The COVID-19 pandemic is rapidly evolving and changing the landscape of cancer care. Young people living with cancer are a unique population and might be more vulnerable during this time in comparison with their healthy peers. There is a need to screen for psychological distress and attend to young people whose cancer care has been delayed. As the lockdown begins to ease, the guidelines about cancer care should be updated according to this population's needs.

Changes in opioid prescribing during the COVID-19 pandemic in England: an interrupted time-series analysis in the OpenSAFELY-TTP cohort.

BACKGROUND: The COVID-19 pandemic disrupted health-care delivery, including difficulty accessing in-person care, which could have increased the need for strong pharmacological pain relief. Due to the risks associated with overprescribing of opioids, especially to vulnerable populations, we aimed to quantify changes to measures during the COVID-19 pandemic, overall, and by key subgroups. METHODS: For this interrupted time-series analysis study conducted in England, with National Health Service England approval, we used routine clinical data from more than 20 million general practice adult patients in OpenSAFELY-TPP, which is a a secure software platform for analysis of electronic health records. We included all adults registered with a primary care practice using TPP-SystmOne software. Using interrupted time-series analysis, we quantified prevalent and new opioid prescribing before the COVID-19 pandemic (January, 2018-February, 2020), during the lockdown (March, 2020-March, 2021), and recovery periods (April, 2021-June, 2022), overall and stratified by demographics (age, sex, deprivation, ethnicity, and geographical region) and in people in care homes identified via an address-matching algorithm. FINDINGS: There was little change in prevalent prescribing during the pandemic, except for a temporary increase in March, 2020. We observed a 9·8% (95% CI -14·5 to -6·5) reduction in new opioid prescribing from March, 2020, with a levelling of the downward trend, and rebounding slightly after April, 2021 (4·1%, 95% CI -0·9 to 9·4). Opioid prescribing rates varied by demographics, but we found a reduction in new prescribing for all subgroups except people aged 80 years or older. Among care home residents, in April, 2020, parenteral opioid prescribing increased by 186·3% (153·1 to 223·9). INTERPRETATION: Opioid prescribing increased temporarily among older people and care home residents, likely reflecting use to treat end-of-life COVID-19 symptoms. Despite vulnerable populations being more affected by health-care disruptions, disparities in opioid prescribing by most demographic subgroups did not widen during the pandemic. Further research is needed to understand what is driving the changes in new opioid prescribing and its relation to changes to health-care provision during the pandemic. FUNDING: The Wellcome Trust, Medical Research Council, The National Institute for Health and Care Research, UK Research and Innovation, and Health Data Research UK.

Changes in cognitive processes and coping strategies precede changes in symptoms during cognitive therapy for posttraumatic stress disorder.

Theories of posttraumatic stress disorder (PTSD) highlight the role of cognitive and behavioral factors in its development, maintenance, and treatment. This study investigated the relationship between changes in factors specified in Ehlers and Clark's (2000) model of PTSD and PTSD symptom change in 217 patients with PTSD who were treated with cognitive therapy for PTSD (CT-PTSD) in routine clinical care. Bivariate latent change score models (LCSM) of session-by-session changes in self-report measures showed that changes in PTSD symptoms were preceded by changes in negative appraisals, flashback characteristics of unwanted memories, safety behaviours, and unhelpful responses to intrusions, but not vice versa. For changes in trauma memory disorganization and PTSD symptoms we found a bidirectional association. This study provides evidence that cognitive and behavioral processes proposed in theoretical models of PTSD play a key role in driving symptom improvement during CT-PTSD.

OpenSAFELY NHS Service Restoration Observatory 2: changes in primary care clinical activity in England during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible. AIM: To describe changes in the volume and variation of coded clinical activity in general practice across six clinical areas: cardiovascular disease, diabetes, mental health, female and reproductive health, screening and related procedures, and processes related to medication. DESIGN AND SETTING: With the approval of NHS England, a cohort study was conducted of 23.8 million patient records in general practice, in situ using OpenSAFELY. METHOD: Common primary care activities were analysed using Clinical Terms Version 3 codes and keyword searches from January 2019 to December 2020, presenting median and deciles of code usage across practices per month. RESULTS: Substantial and widespread changes in clinical activity in primary care were identified since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health (for example, for 'Depression interim review' the median occurrences across practices in December 2020 was down by 41.6% compared with December 2019). CONCLUSION: Granular NHS general practice data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for the key measures identified in this study, as well as further studies using primary care data to monitor and mitigate the indirect health impacts of COVID-19 on the NHS.

Eleven key measures for monitoring general practice clinical activity during COVID-19: A retrospective cohort study using 48 million adults' primary care records in England through OpenSAFELY.

Background: The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic. Methods: With the approval of NHS England, we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults.We developed SNOMED-CT codelists for key measures of primary care clinical activity such as blood pressure monitoring and asthma reviews, selected by an expert clinical advisory group and conducted a population cohort-based study to describe trends and variation in these measures January 2019-December 2021, and pragmatically classified their level of recovery one year into the pandemic using the percentage change in the median practice level rate. Results: We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021. Conclusions: The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data. Funding: This research used data assets made available as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058).The OpenSAFELY Platform is supported by grants from the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157).

Trends, variation, and clinical characteristics of recipients of antiviral drugs and neutralising monoclonal antibodies for covid-19 in community settings: retrospective, descriptive cohort study of 23.4 million people in OpenSAFELY.

Objective: To ascertain patient eligibility status and describe coverage of antiviral drugs and neutralising monoclonal antibodies (nMAB) as treatment for covid-19 in community settings in England. Design: Retrospective, descriptive cohort study, approved by NHS England. Setting: Routine clinical data from 23.4 million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database. Participants: Outpatients with covid-19 at high risk of severe outcomes. Interventions: Nirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units. Results: 93 870 outpatients with covid-19 were identified between 11 December 2021 and 28 April 2022 to be at high risk of severe outcomes and therefore potentially eligible for antiviral or nMAB treatment (or both). Of these patients, 19 040 (20%) received treatment (sotrovimab, 9660 (51%); molnupiravir, 4620 (24%); paxlovid, 4680 (25%); casirivimab/imdevimab, 50 (<1%); and remdesivir, 30 (<1%)). The proportion of patients treated increased from 9% (190/2220) in the first week of treatment availability to 29% (460/1600) in the latest week. The proportion treated varied by high risk group, being lowest in those with liver disease (16%; 95% confidence interval 15% to 17%); by treatment type, with sotrovimab favoured over molnupiravir and paxlovid in all but three high risk groups (Down's syndrome (35%; 30% to 39%), rare neurological conditions (45%; 43% to 47%), and immune deficiencies (48%; 47% to 50%)); by age, ranging from ≥80 years (13%; 12% to 14%) to 50-59 years (23%; 22% to 23%); by ethnic group, ranging from black (11%; 10% to 12%) to white (21%; 21% to 21%); by NHS region, ranging from 13% (12% to 14%) in Yorkshire and the Humber to 25% (24% to 25%) in the East of England); and by deprivation level, ranging from 15% (14% to 15%) in the most deprived areas to 23% (23% to 24%) in the least deprived areas. Groups that also had lower coverage included unvaccinated patients (7%; 6% to 9%), those with dementia (6%; 5% to 7%), and care home residents (6%; 6% to 7%). Conclusions: Using the OpenSAFELY platform, we were able to identify patients with covid-19 at high risk of severe outcomes who were potentially eligible to receive treatment and assess the coverage of these new treatments among these patients. In the context of a rapid deployment of a new service, the NHS analytical code used to determine eligibility could have been over-inclusive and some of the eligibility criteria not fully captured in healthcare data. However targeted activity might be needed to resolve apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, ethnic groups, people aged ≥80 years, those living in socioeconomically deprived areas, and care home residents.

lcsm: An R package and tutorial on latent change score modelling.

Latent change score models (LCSMs) are used across disciplines in behavioural sciences to study how constructs change over time. LCSMs can be used to estimate the trajectory of one construct (univariate) and allow the investigation of how changes between two constructs (bivariate) are associated with each other over time. This paper introduces the R package lcsm, a tool that aims to help users understand, analyse, and visualise different latent change score models. The lcsm package provides functions to generate model syntax for basic univariate and bivariate latent change score models with different model specifications. It is also possible to visualise different model specifications in simplified path diagrams. An interactive application illustrates the main functions of the package and demonstrates how the model syntax and path diagrams change based on different model specifications. This R package aims to increase the transparency of reporting analyses and to provide an additional resource to learn latent change score modelling.

The Relationship Between Working Alliance and Symptom Improvement in Cognitive Therapy for Posttraumatic Stress Disorder.

Background: Working alliance has been shown to predict outcome of psychological treatments in multiple studies. Conversely, changes in outcome scores have also been found to predict working alliance ratings. Objective: To assess the temporal relationships between working alliance and outcome in 230 patients receiving trauma-focused cognitive behavioral treatment for posttraumatic stress disorder (PTSD). Methods: Ratings of working alliance were made by both the patient and therapist after sessions 1, 3, and 5 of a course of Cognitive Therapy for PTSD (CT-PTSD). Autoregressive, cross-lagged panel models were used to examine whether working alliance predicted PTSD symptom severity at the next assessment point and vice versa. Linear regressions tested the relationship between alliance and treatment outcome. Results: Both patients' and therapists' working alliance ratings after session 1 predicted PTSD symptom scores at the end of treatment, controlling for baseline scores. At each assessment point, higher therapist working alliance was associated with lower PTSD symptoms. Crossed-lagged associations were found for therapist-rated alliance, but not for patient-rated alliance: higher therapists' alliance ratings predicted lower PTSD symptom scores at the next assessment point. Similarly, lower PTSD symptoms predicted higher therapist working alliance ratings at the next assessment point. Ruminative thinking was negatively related to therapists' alliance ratings. Conclusions: Working alliance at the start of treatment predicted treatment outcome in patients receiving CT-PTSD and may be an important factor in setting the necessary conditions for effective treatment. For therapists, there was a reciprocal relationship between working alliance and PTSD symptom change in their patients during treatment, suggesting that their alliance ratings predicted symptom change, but were also influenced by patients' symptom change.

Cognitive Mechanisms in Adolescent and Young Adult Cancer Patients and Survivors: Feasibility and Preliminary Insights from the Cognitions and Affect in Cancer Resiliency Study.

This cross sectional pilot study assesses the feasibility of conducting online research into cognitive mechanisms in adolescent and young adult cancer populations. Twenty-one participants, aged 18-39 years, answered questionnaires about mental defeat, rumination, cancer worry, anxiety, and experience participating in such research. Seven participants scored in the clinical range for anxiety. Cancer-related worry was common. Rumination and mental defeat were positively associated with anxiety. The participants reported the length and type of questions to be appropriate and not distressing. Findings may inform future research into cognitive mechanisms, which could aid the development of psychosocial interventions for young cancer patients.

suddengains: An R package to identify sudden gains in longitudinal data.

Sudden gains are large and stable improvements in an outcome variable between consecutive measurements, for example during a psychological intervention with multiple assessments. Researching these occurrences could help understand individual change processes in longitudinal data. Three criteria are generally used to identify sudden gains in psychological interventions. However, applying these criteria can be time consuming and prone to errors if not fully automated. Adaptations to these criteria and methodological decisions such as how multiple gains are handled vary across studies and are reported with different levels of detail. These problems limit the comparability of individual studies and make it hard to understand or replicate the exact methods used. The R package suddengains provides a set of tools to facilitate sudden gains research. This article illustrates how to use the package to identify sudden gains or sudden losses and how to extract descriptive statistics as well as exportable data files for further analysis. It also outlines how these analyses can be customised to apply adaptations of the standard criteria. The suddengains package therefore offers significant scope to improve the efficiency, reporting, and reproducibility of sudden gains research.

Cognitive processes associated with sudden gains in cognitive therapy for posttraumatic stress disorder in routine care.

OBJECTIVE: Although most studies investigating sudden gains in treatments for posttraumatic stress disorder (PTSD) report a positive association between sudden gains and outcomes at the end of treatment, less is known about sudden gains in routine clinical care and the processes involved in their occurrence. This study investigated changes in cognitive factors (negative appraisals, trauma memory characteristics) before, during, and after sudden gains in PTSD symptom severity. METHOD: Two samples (N1 = 248, N2 = 234) of patients who received trauma-focused cognitive therapy for PTSD in routine clinical care were analyzed. Mahalanobis distance matching, including the propensity score, was used to compare patients with sudden gains and similar patients without sudden gains. Estimates from both samples were meta-analyzed to obtain pooled effects. RESULTS: Patients with sudden gains (n1 = 76, n2 = 87) reported better treatment outcomes in PTSD symptom severity, depression, and anxiety at the end of therapy and follow-up than those without sudden gains. No baseline predictors of sudden gains could be reliably identified. During sudden gains, those with sudden gains had greater changes in both cognitive factors than matched patients. Meta-analyses of the two samples showed that negative appraisals had already decreased in the session prior to sudden gains compared with matched patients. CONCLUSIONS: The pooled estimates suggest that changes in negative trauma-related appraisals precede sudden gains in PTSD symptoms. The results suggest that interventions that promote change in appraisals may also facilitate sudden gains in therapy. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Internet-delivered cognitive therapy for PTSD: a development pilot series.

BACKGROUND: Randomised controlled trials have established that face-to-face cognitive therapy for posttraumatic stress disorder (CT-PTSD) based on Ehlers and Clark's cognitive model of PTSD is highly effective and feasible with low rates of dropout. Access to evidence-based psychological treatments for PTSD is insufficient. Several studies have shown that therapist-assisted treatment delivery over the Internet is a promising way of improving access to cognitive behavioural therapy interventions. OBJECTIVE: To develop an Internet version of CT-PTSD that significantly reduces therapist contact time without compromising treatment integrity or retention rates. METHODS: We describe the development of an Internet version of CT-PTSD. It implements all the key procedures of face-to-face CT-PTSD, including techniques that focus on the trauma memory, such as memory updating, stimulus discrimination and revisiting the trauma site, as well as restructuring individually relevant appraisals relating to overgeneralisation of danger, guilt, shame or anger, behavioural experiments and planning activities to reclaim quality of life. A cohort of 10 patients meeting DSM-IV criteria for PTSD worked through the programme, with remote guidance from a therapist, and they were assessed at pre- and post-treatment on PTSD outcome, mood, work and social adjustment and process measures. RESULTS: No patients dropped out. Therapists facilitated the treatment with 192 min of contact time per patient, plus 57 min for reviewing the patient's progress and messages. Internet-delivered CT-PTSD was associated with very large improvements on all outcome and process measures, with 80% of patients achieving clinically significant change and remission from PTSD. CONCLUSIONS: Internet-delivered cognitive therapy for PTSD (iCT-PTSD) appears to be an acceptable and efficacious treatment. Therapist time was reduced to less than 25% of time in face-to-face CT-PTSD. Randomised controlled trials are required to evaluate systematically the acceptability and efficacy of iCT-PTSD.