The Smiley Faces task and how it can help teach some fundamentals for good clinical trials

Background: Many factors need to be considered when designing a clinical trial. Although structures such as PICOT (Population, Intervention, Comparator, Outcome, Timeline) are helpful, people with little or no prior knowledge can find designing and implementing a trial to be overly complicated. We developed a simple exercise to illustrate key features of trials: the Smiley Faces task.Aim: We describe how the Smiley Faces task can demonstrate the importance of good planning of trials and highlight pitfalls.Method and Results: The Smiley Faces task is centred on the simple, intuitive task to “draw a smiley face”. It requires no existing knowledge about trials or research generally, but can be used to highlight key features of a trial; such as formulating the research question; planning for coding, collection and analysis of data; handling of missing data and drawing of conclusions. We present insights from conducting the exercise dozens of times and collecting hundreds of smiley face drawings in a range of educational settings.Conclusion: The simplicity and accessibility of the task makes it relatively easy to demonstrate key points for careful planning of clinical trials. The approach is generalizable and applicable to researchers and teachers in a variety of medical settings

Impact of the COVID-19 pandemic on commencement of psychotropic medications in Northern Ireland: a population-wide, administrative data linkage study.

Objectives This study aimed to explore changes in commencement of psychotropic medications in first 20 months of the pandemic and associated restrictions in Northern Ireland (NI). Approach Antidepressant, anxiolytic, hypnotic and antipsychotic medications dispensed in all community pharmacies in NI (Jan-2012 to Oct-2021, Enhanced Prescribing Database) were linked to sociodemographic data (National Health Application and Infrastructure Services) for everyone alive and resident in NI aged ≥10years. Commencement of new medication was identified on a rolling monthly basis as a dispensation in a given month but not in the previous 24 months. Auto Regressive Integrated Moving Average (ARIMA) models were trained taking trends and seasonal effects into consideration. Monthly forecasts were compared to actual numbers, at population level and within sociodemographic groups (gender, age, rurality, living-alone, deprivation). Results There were consistent increased numbers of individuals commencing antipsychotic medications in the group aged ≥65years, with observed to expected ratio ranging from 1.12 to 2.1.  Commencement of hypnotics was decreased throughout the study in individuals aged <18years (OER ranged from 0.28 to 0.70) but remained as expected for other sociodemographic groups.  Across all sociodemographic groups, commencement of antidepressants decreased initially (Mar-May 2020 population-level OER ranged from 0.61 to 0.79) and in Jan 2021 (population-level OER 0.78) corresponding with stricter stay at home restrictions but resumed the expected trend outside of these periods.  There were no obvious deviations from expected trends in commencement of anxiolytics. Conclusion There was a clear impact on older people with regards commencement of antipsychotic medications throughout the pandemic. Hypnotic commencement in children was lower than expected throughout the pandemic, which may reflect reduced need or reduced access to specialist paediatric services. (NHS-REC:20/YH/0254; Data sourced from the Honest Broker Service

Sleep Medication Use by people with Cerebral Palsy: A Population Level DataLinkage Study

Objectives To (1) compare proportions of the population dispensed sleep medication, and rate (dispensations/month) and amount (milligrams/month) of dispensed sleep medication, in individuals with and without cerebral palsy (CP); and (2) describe dispensation of sleep medication within CP and non-CP cohorts with respect to sociodemographic and clinical characteristics. Approach Individuals aged 6 -36 years (aligning with those known to the Northern Ireland CP Register [NICPR]), registered with a general practitioner at 01-January-2018, were identified within the National Health Application and Infrastructure System.  Sleep medications dispensed 01-January-2018 to 31-December-2019 were extracted from the Enhanced Prescribing Database.  Analysis was limited to melatonin due to small counts in other medications.  Routine healthcare data was sourced from the Honest Broker Service (HBS).  NICPR clinical data (CP-type, Gross Motor Function Classification System (GMFCS), gestation and birthweight) were linked to routine healthcare data using the Health and Care Number by HBS. Descriptive statistics are presented. Results Complete matching was achieved between NICPR and healthcare data using the HCN.  Final cohorts consisted of 1,598 individuals with CP and 790,097 without CP. A greater proportion of those with CP were dispensed melatonin compared to those without CP (4.6% vs 1.0%).  The CP cohort were also dispensed melatonin at a greater rate (median(IQR) CP 0.33(0.71) vs non-CP 0.25(0.54) dispensations/month) and in greater amounts (median(IQR) CP 30(74.7) vs non-CP 17.5(55.0) mg/month).  Within the CP cohort, differences in melatonin dispensation were observed across sociodemographic groups (male 5.1% vs female 3.9%; children 8.2% vs young adults 2.2%; urban 6.5% vs rural 5.0%); deprived 5.1% vs affluent 4.2%).  Clinical characteristics associated with greatest dispensation of melatonin were non-spastic CP (6.83%), GMFCS IV&V (5.29%), or extremely premature birth (6.85%). Conclusion Individuals with CP, particularly children, are more likely to be dispensed sleep medications compared to the general population.  Awareness of this disparity could encourage further research on assessment and management of sleep in CP and facilitate discussions between healthcare providers and families on underlying causes of sleep problems

Analyses of ionizing radiation effects in – vitro in peripheral blood 1 lymphocytes with Raman spectroscopy

The use of Raman spectroscopy to measure the biochemical profile of healthy and diseased cells and tissues may be a potential solution to many diagnostic problems in the clinic. Although extensively used to identify changes in the biochemical profiles of cancerous cells and tissue, Raman spectroscopy has been used less often for analyzing changes to the cellular environment by external factors such as ionizing radiation. In tandem with this, the biological impact of low doses of ionizing radiation remains poorly understood. Extensive studies have been performed on the radiobiological effects associated with radiation doses above 0.1 Gy, and are well characterized, but recent studies on low-dose radiation exposure have revealed complex and highly variable responses. We report here the novel finding that demonstrate the capability of Raman spectroscopy to detect radiation-induced damage responses in isolated lymphocytes irradiated with doses of 0.05 and 0.5 Gy. Lymphocytes were isolated from peripheral blood in a cohort of volunteers, cultured ex vivo and then irradiated. Within 1 h after irradiation spectral effects were observed with Raman microspectroscopy and principal component analysis and linear discriminant analysis at both doses relative to the sham-irradiated control (0 Gy). Cellular DNA damage was confirmed using parallel γ-H2AX fluorescence measurements on the extracted lymphocytes per donor and per dose. DNA damage measurements exhibited interindividual variability among both donors and dose, which matched that seen in the spectral variability in the lymphocyte cohort. Further evidence of links between spectral features and DNA damage was also observed, which may potentially allow noninvasive insight into the DNA remodeling that occurs after exposure to ionizing radiation

Long-lasting effects of methocinnamox on opioid self-administration in rhesus monkeys

Opioid abuse remains a serious public health challenge, despite the availability of medications that are effective in some patients (naltrexone, buprenorphine, and methadone). This study explored the potential of a pseudoirreversible mu-opioid receptor antagonist [methocinnamox (MCAM)] as a treatment for opioid abuse by examining its capacity to attenuate the reinforcing effects of mu-opioid receptor agonists in rhesus monkeys. In one experiment, monkeys responded for heroin (n 5 5) or cocaine (n 5 4) under a fixed-ratio schedule. Another group (n 5 3) worked under a choice procedure with one alternative delivering food and the other alternative delivering the mu-opioid receptor agonist remifentanil. A third group (n 5 4) responded for food and physiologic parameters were measured via telemetry. The effects of MCAM were determined in all experiments and, in some cases, were compared with those of naltrexone. When given immediately before sessions, naltrexone dose-dependently decreased responding for heroin and decreased choice of remifentanil while increasing choice of food, with responding returning to baseline levels 1 day after naltrexone injection. MCAM also decreased responding for heroin and decreased choice of remifentanil while increasing choice of food; however, opioid-maintained responding remained decreased for several days after treatment. Doses of MCAM that significantly decreased opioid-maintained responding did not decrease responding for cocaine or food. MCAM did not impact heart rate, blood pressure, body temperature, or activity at doses that decreased opioid self-administration. Because MCAM selectively attenuates opioid self-administration for prolonged periods, this novel drug could be a safe and effective alternative to currently available treatments for opioid abuse.</p

Changing trends in child welfare inequalities in Northern Ireland

Objectives This study uses longitudinal administrative data to investigate the relationship between area level deprivation and the 1) referral, 2) investigation, 3) registration and 4) looked-after stages of children’s contact with child and family social work in Northern Ireland (NI) from 2010-2017 (stages 1-3) and 2010-2020 (stage 4). Methods Children’s social care data (SOSCARE database) for the years 2010 to 2020 were obtained from the Honest Broker Service in NI. The data were linked with the 2017 NI Multiple Deprivation Measure through the family of origin postcode. Cross-tabulations of year and deprivation decile were used to produce frequencies of children who experienced the four levels of intervention within each of the study years. These were then used to calculate various measures of absolute and relative inequality including the Slope Index of Inequality (SII), the Relative Ratio of Inequality (RRI) and the Relative Index of Inequality (RII). Results There was a clear and increasing social gradient in child welfare interventions over time. Children referred to children’s social care during 2010-2017 were 4-5 times more likely to come from the most deprived areas compared to the least deprived. Despite fairly stable levels of referral inequality, the ratio of children subject to child protection investigations rose from 3 in 2010 to 6 in 2017, the ratio of children subject to child protection plans rose from 4.5 in 2010 to 8 in 2017 and the ratio of children looked after rose from 4 in 2010 to 9 in 2020. This widening inequality was largely driven by the increasing involvement of younger children from the most deprived areas in child protection and looked-after processes. Conclusion In an environment of economic austerity and reduced spending, we are intervening in the lives of children and families living in the most deprived areas of NI at disproportionate rates. The current independent review of children’s social care offers an opportunity to reconfigure current provision with a clear inequalities focus

Relationship and attachment to digital health technology during cancer treatment

Objective The aim of this study is to explore the relationship that people with cancer and their family caregivers develop with symptom management technology during chemotherapy. Data Sources A longitudinal and multi-perspective interpretative phenomenological approach was adopted. Data were collected using one-to-one in-depth interviews with people with colorectal cancer using supportive digital health symptom management technology (n=3) and their family caregivers (n=4) at two time points during chemotherapy treatment. Data were analyzed using interpretative phenomenological analysis and followed COREQ guidelines. Conclusion People with cancer and their family caregivers can develop emotional bonds with supportive symptom management technology during cancer treatment. Digital health technology can be experienced as a person guiding them during their cancer treatment. Participants felt vulnerable after the technology was returned to the research team. Participants recognized that it was not the technology that successfully facilitated them through their initial chemotherapy cycles; rather, the technology helped them learn to manage their symptoms and promoted their self-efficacy, as well as how to emotionally respond. Implications for Nursing Practice: The relationship and psychological bonds people with cancer and their family caregivers develop with technology during treatment may be critically important for oncology nurses to be aware of should digital health be prescribed within the outpatient model of cancer care. This study indicates that technology may not be needed for a full treatment experience, as digital health can promote confidence and self-efficacy regarding symptom management and prepare people with cancer to be independent after the digital health technology is returned to the research team. However, further research is needed regarding individual preferences for digital health provision