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Patient and public involvement (PPI) plays a crucial role in ensuring research is carried out in conjunction with the people that it will impact upon. In this article, we present our experiences and reflections from working collaboratively with patients and public through the lifetime of an National Institute for Health Research (NIHR) programme grant; the Chronic Headache Education and Self-management Study (CHESS) which took place between 2015 and 2020.
PPI over the course of CHESS:
We worked closely with three leading UK migraine charities and a lay advisory group throughout the programme. We followed NIHR standards and used the Guidance for Reporting Involvement of Patients and the Public checklist. We consulted our PPI contacts using a variety of methods depending on the phase of the study and the nature of the request. This included emails, discussions, and face-to-face contact.
PPI members contributed throughout the study in the programme development, in the grant application, ethics documentation, and trial oversight. During the feasibility study; in supporting the development of a classification interview for chronic headache by participating in a headache classification conference, assessing the relevance, and acceptability of patient-reported outcome measures by helping to analyse cognitive interview data, and testing the smartphone application making suggestions on how best to present the summary of data collected for participants. Due to PPI contribution, the content and duration of the study intervention were adapted and a Delphi study with consensus meeting developed a core outcome set for migraine studies.
The involvement of the public and patients in CHESS has allowed us to shape its overall design, intervention development, and establish a core outcome set for future migraine studies. We have reflected on many learning points for the future application of PPI.
Panic disorder (PD) is a prevalent and impairing anxiety disorder with previous reports suggesting that the longer the condition remains untreated, the greater the likelihood of nonresponse. However, patients with PD may wait for years before receiving a guideline-recommended pharmacological treatment. The widespread prescription of benzodiazepines (BDZ) for managing anxiety symptoms and disorders might delay the administration of pharmacotherapy according to guidelines (eg, selective serotonin reuptake inhibitors, SSRIs). The present study aimed to determine the mean duration of untreated illness (DUI) in a sample of PD patients, to quantify and compare DUI-SSRI to DUI-BDZ, and to compare findings with those from previous investigations.
Three hundred and fourteen patients with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition diagnosis of PD were recruited from an Italian outpatient psychotherapy unit, and epidemiological and clinical variables were retrieved from medical records. Descriptive statistical analyses were undertaken for sociodemographic and clinical variables, Wilcoxon matched-pair signed rank test was applied to compare the distribution of DUI-SSRI vs DUI-BDZ, and Welch’s t test was performed to compare findings with those from previous studies.
The mean DUI-SSRI of the total sample was 64.25 ± 112.74 months, while the mean DUI-BDZ was significantly shorter (35.09 ± 78.62 months; P < 0.0001). A significantly longer DUI-SSRI, compared to findings from previous studies, was also observed.
The present results confirm a substantial delay in implementing adequate pharmacological treatments in patients with PD, and highlight the discrepancy between recommendations from international treatment guidelines and common clinical practice in relation to BDZ prescription.
The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.
Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.
The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.
The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.
Front-of-pack (FOP) nutrition labelling is a globally recommended strategy to encourage healthier food choices. We evaluated the effect of FOP labels on the perceived healthfulness of a sweetened fruit drink in an international sample of adult consumers.
Six-arm randomised controlled experiment to examine the impact of FOP labels (no label control, Guideline Daily Amounts (GDA), Multiple Traffic Lights, the Health Star Ratings (HSR), Health Warning Labels, and ‘High-in’ Warning Labels (HIWL)) on the perceived healthfulness of the drink. Linear regression models by country examined healthfulness perceptions on FOP nutrition labels, testing for interactions by demographic characteristics.
Online survey in 2018 among participants from Australia, Canada, Mexico, United Kingdom (UK) and United States.
Adults (≥18 years, n 22 140).
Compared with control, HIWL had the greatest impact in lowering perceived healthfulness (β from −0·62 to −1·71) across all countries. The HIWL and the HSR had a similar effect in Australia. Other labels were effective in decreasing the perceived healthfulness of the drink within some countries only, but to a lower extent. The GDA did not reduce perceived healthfulness in most countries. In the UK, the effect of HIWL differed by age group, with greater impact among older participants (> 40 years). There were no other variations across key demographic characteristics.
HIWL, which communicates clear, non-quantitative messages about high levels of nutrients of concern, demonstrated the greatest efficacy to decrease the perceived healthfulness of a sweetened fruit drink across countries. This effect was similar across demographic characteristics.
Cancer-related dyspnea is a common symptom in patients with cancer. It has also been reported to be a predictor of poorer prognosis, which can then change clinical treatment and advance care planning. Currently, no definitive recommendation for pharmacologic agents for cancer-related dyspnea exists. The aim of this systematic review and network meta-analysis is to compare pharmacologic agents for the prophylaxis and treatment of cancer-related dyspnea.
A search was conducted in the databases of PubMed, Embase, and Cochrane CENTRAL through May 2021. Standardized mean differences (SMDs), as reported by studies or calculated from baseline and follow-up dyspnea scores, were amalgamated into a summary SMD and 95% confidence interval (CI) using a restricted maximum likelihood multivariate network meta-analysis.
Twelve studies were included in this review; six reported on prophylaxis of exertional dyspnea, five on treatment of everyday dyspnea, and one on treatment of episodic dyspnea. Morphine sulfate was better at controlling everyday dyspnea than placebo (SMD 1.210; 95% CI: 0.415–2.005). Heterogeneity in study design and comparisons, however, led to some concerns with the underlying consistency assumption in network meta-analysis design.
Optimal pharmacologic interventions for cancer-related dyspnea could not be determined based on this analysis. Further trials are needed to report on the efficacy of pharmacologic interventions for the prophylaxis and treatment of cancer-related dyspnea.
Approximately 60 000 people in England have coexisting type 2 diabetes mellitus (T2DM) and severe mental illness (SMI). They are more likely to have poorer health outcomes and require more complex care pathways compared with those with T2DM alone. Despite increasing prevalence, little is known about the healthcare resource use and costs for people with both conditions.
To assess the impact of SMI on healthcare resource use and service costs for adults with T2DM, and explore the predictors of healthcare costs and lifetime costs for people with both conditions.
This was a matched-cohort study using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics for 1620 people with comorbid SMI and T2DM and 4763 people with T2DM alone. Generalised linear models and the Bang and Tsiatis method were used to explore cost predictors and mean lifetime costs respectively.
There were higher average annual costs for people with T2DM and SMI (£1930 higher) than people with T2DM alone, driven primarily by mental health and non-mental health-related hospital admissions. Key predictors of higher total costs were older age, comorbid hypertension, use of antidepressants, use of first-generation antipsychotics, and increased duration of living with both conditions. Expected lifetime costs were approximately £35 000 per person with both SMI and T2DM. Extrapolating nationally, this would generate total annual costs to the National Health Service of around £250 m per year.
Our estimates of resource use and costs for people with both T2DM and SMI will aid policymakers and commissioners in service planning and resource allocation.
Telehealth has the potential to address health disparities, but not without deliberate choices about how to implement it. To support vulnerable patients, health policy leaders must pursue creative solutions such as public-private partnerships, broadband infrastructure, and value-based payment. Without these initiatives or others like them, health disparities are likely to persist despite telehealth’s tantalizing potential.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Within the family Adeleidae, Adelina spp. belong to a group of arthropod pathogens. These parasites have been reported to have a wide geographic distribution, however, there are no reports of these protists in the Canary Islands, Spain. One of the peculiarities of the life cycle of Adelina spp. is the participation of a predator, because fecundation and sporulation occur inside the body cavity, and so necessitate destruction of the definitive host. The involvement therefore of a ‘dispersion host’, which eats the definitive host and spreads the oocysts through its faeces, is critical for the maintenance of certain Adelina spp. On the island of Gran Canaria, adeleid oocysts have been found in stool samples from four animals, three California kingsnakes (Lampropeltis californiae), and one feral cat. These animals were part of a larger coprological study of vertebrate parasites (117 snakes, 298 cats), where pseudoparasitic elements were also recorded. L. californiae and feral cats are invasive species which are widespread across the island and this novel finding of Adelina spp. oocysts in their faeces suggests that they could also serve as potential sentinel species for arthropod parasites.
To explore the theory of wellbeing and to propose an operational definition for wellbeing in doctors.
Hypothesis: An operational definition for wellbeing in doctors is needed in order for it to be measured and interventions to improve it developed.
There is no internationally recognised definition for wellbeing and yet wellbeing is an increasingly fashionable topic of research and development, including in doctors. This is because wellbeing can be described using either hedonist, or eudonist philosophy and there is a lack of conceptual clarity about what wellbeing is, and how it works. Research into the measurement of mental wellbeing has been dominated by individualist societies, with the inherent bias towards measuring self-centred components and not the other-orientated components that might be valued more in collectivist societies and by doctors.
The Centre for Workforce Wellbeing (C4WW), a collaboration between the University of Southampton and Health Education England, was created to support research into the nature, assessment and enhancement of wellbeing in physicians. A literature review of the philosophy, definition and measurement of wellbeing was undertaken with a focus on mental wellbeing at work and specifically in doctors.
A concept map of the relationship between wellbeing terms has been created and was used to understand and classify where mental wellbeing itself was being defined and measured in studies, as opposed to a component of wellbeing, or determinant of wellbeing. Thematic analysis was used to develop an operational definition of wellbeing for doctors.
Measurement of wellbeing and interventions for wellbeing cannot be developed if you cannot clearly define what wellbeing is. An operational definition of mental wellbeing in doctors is ethically required to prevent research waste and to allow us to identify and recreate when doctors thrive, not just survive.
To achieve a consensus Core Outcome Set for measuring mental wellbeing in doctors.
Hypothesis: A minimum set of valid, reliable and practical wellbeing measures is needed for doctors.
The importance of doctors’ mental wellbeing to everyone using Health Care is highlighted by the levels of burnout reported in doctors around the world. In 2019 a number of UK policy documents made recommendations for the wellbeing of doctors, but how those wellbeing interventions are evaluated needs to be defined. Core Outcome Sets are increasingly being used in medicine to prevent waste in research, by recommending the inclusion of a minimum set of valid, reliable and practical measures. An operational definition and Core Outcome Set for wellbeing in doctors is needed to meaningfully progress the work in this field.
The Centre for Workforce Wellbeing (C4WW), a collaboration between the University of Southampton and Health Education England, was created to support research into the nature, assessment and enhancement of wellbeing in physicians. A Systematic Review of wellbeing measures used in doctors and the robustness of those measures, along with surveys of 250 UK doctors of all grades and specialities and patient and public involvement is informing what a core outcome set could be. A Delphi Study among 37 UK experts has been initiated to establish the consensus Core Outcome Set.
Publication of research into doctors’ wellbeing is growing internationally. In the UK alone data are being captured by multiple national organisations including: the Care Quality Commission, General Medical Council, British Medical Association and the Royal Colleges. Health and Social Care Organisations are, therefore, keen to “do something” and are spending money on wellbeing interventions with little, or no, evidence base and a lack of appropriate, comparable evaluation. A Core Outcome Set for measuring wellbeing in doctors is ethically required to reduce waste, to replace burnout measures and to refine wellbeing interventions.
Wellbeing measures that actually measure wellbeing, and not burnout, which are validated, reliable and practical, are needed to inform local organisational, national government and international research policy. An absence of burnout does not equate to wellbeing. The focus of measurement needs to shift to capture in what contexts we thrive, not just survive. If everyone used the same Core Outcome Set to measure mental wellbeing, direct comparisons could be made, and money invested, in creating infrastructure, processes and cultures that really work.
Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom non-remission in first-episode psychosis.
Our development cohort consisted of 1027 patients with first-episode psychosis recruited between 2005 to 2010 from 14 early intervention services across the National Health Service in England. Our validation cohort consisted of 399 patients with first-episode psychosis recruited between 2006 to 2009 from a further 11 English early intervention services. The one-year non-remission rate was 52% and 54% in the development and validation cohorts, respectively. Multivariable logistic regression was used to develop a risk prediction model for non-remission, which was externally validated.
The prediction model showed good discrimination (C-statistic of 0.74 (0.72, 0.76) and adequate calibration with intercept alpha of 0.13 (0.03, 0.23) and slope beta of 0.99 (0.87, 1.12). Our model improved the net-benefit by 16% at a risk threshold of 50%, equivalent to 16 more detected non-remitted first-episode psychosis individuals per 100 without incorrectly classifying remitted cases.
Once prospectively validated, our first episode psychosis prediction model could help identify patients at increased risk of non-remission at initial clinical contact.
In his recent book on Property, Power and Politics, Jean-Philippe Robé makes a strong case for the need to understand the legal foundations of modern capitalism. He also insists that it is important to distinguish between firms and corporations. We agree. But Robé criticizes our definition of firms in terms of legally recognized capacities on the grounds that it does not take the distinction seriously enough. He argues that firms are not legally recognized as such, as the law only knows corporations. This argument, which is capable of different interpretations, leads to the bizarre result that corporations are not firms. Using etymological and other evidence, we show that firms are treated as legally constituted business entities in both common parlance and legal discourse. The way the law defines firms and corporations, while the product of a discourse which is in many ways distinct from everyday language, has such profound implications for the way firms operate in practice that no institutional theory of the firm worthy of the name can afford to ignore it.
The Bronze Age in Britain is now a term often used to include both the first use of copper c. 2400 bc and also tin-bronze from c. 2100 bc, all of which required the extensive use of copper. Prehistoric mining for this metal has been identified in surface and underground workings in Parys Mine, Mynydd Parys, Anglesey, although almost all of the surface workings are now obscured by the extensive deep spoil from more recent mining in the industrial period. These copper-bearing ores are in bedded lodes, together with some intruded vein deposits. The Bronze Age workings have been exposed underground where they have been intersected by the early 19th century industrial workings on and above the 16 fathom and 20 fathom levels in the Parys Mine. Spoil exposures contain stone hammers (‘mauls’), wood fragments, and charcoal; samples of the latter have been radiocarbon dated with chronological modelling suggesting activity took place in the first half of the 2nd millennium cal bc. Although relatively limited in extent, these important prehistoric mining sites are among the earliest found in the UK. They have survived due to their protection from surface erosion and limited accessibility.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
This article documents how the COVID-19 crisis has affected the drinking behavior of Latin European wine consumers. Using a large online survey conducted during the first lockdown in France, Italy, Portugal, and Spain (n = 7,324 individuals), we reconstruct the purchasing and consumption patterns of the respondents. The number of people who maintained their wine consumption frequency is significantly higher than those who increased or decreased their consumption. Wine consumption frequency held up better than other types of alcohol (beer and spirits). We analyze heterogeneities among countries and individuals by employing the Marascuilo procedure and an ordered logit model. The latter identifies the impact of demographic, commercial, and psychosocial factors on wine consumption frequency. The results shed light on changes in wine consumer behavior during the first lockdown and consider possible post-lockdown trends that could be useful to industry players. (JEL Classifications: D5, L66, Q1)
During COVID-19, health provision and information resources have been increasingly provided via digital means (e.g. websites, apps) and this will become a standard practice beyond the pandemic. People with severe mental illness face profound health inequalities (e.g. a >20-year mortality gap). Digital exclusion puts this population at risk of heightened or compounded inequalities. This has been referred to as the ‘digital divide’. For any new digital means introduced in clinical practice to augment healthcare service provision, issues of accessibility, acceptability and usability should be addressed by researchers and developers early in the design phase, and prior to full implementation, to prevent digital exclusion.
This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care.
We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted.
Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3–4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3–4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions.
When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.