Pre-notification and reminder SMS text messages with behaviourally informed invitation letters to improve uptake of NHS Health Checks: a factorial randomised controlled trial

Background The NHS Health Check (NHS HC) is a cardiovascular risk assessment to prevent cardiovascular disease. Public Health England (PHE) wants to increase uptake. Methods We explored the impact of behaviourally informed invitation letters and pre-notification and reminder SMS on uptake of NHS HCs. Patients at 28 General Practices in the London Borough of Southwark who were eligible to receive an NHS HC between 1st November 2013 and 31st December 2014 were included. A double-blind randomised controlled trial with a mixed 2 (pre-notification SMS – yes or no) × 4 (letter – national template control, open-ended, time-limited, social norm) × 2 (reminder SMS – yes or no) factorial design was used. The open-ended letter used simplification, behavioural instruction and a personalised planning prompt for patients to record the date and time of their NHS HC. The time-limited letter was similar but stated the NHS HC was due in a named forthcoming month. The social norms letter was similar to the open-ended letter but included a descriptive social norms message and testimonials from local residents and no planning prompt. The outcome measure was attendance at an NHS HC. Results Data for 12, 244 invites were analysed. Uptake increased in almost all letter and SMS combinations compared to the control letter without SMS (Uptake 18%), with increases of up to 12 percentage points for the time-limited letter with pre-notification and reminder (Uptake 30%; Adjusted Odds Ratio AOR 1.86; 95% CI 1.45–2.83; p < 0.00); 10 percentage points for the open-ended letter with reminder (Uptake 27%; AOR 1.68; 95% CI 1.31–2.17; p < 0.00) and a 9 percentage point increase using the time-limited letter with reminder (Uptake 27%; AOR 1.61; 95% CI 1.25–2.10; p < 0.00). The reminder SMS increased uptake for all intervention letters. The pre-notification did not add to this effect. Conclusions This large randomised controlled trial adds support to the evidence that small, low cost behaviourally informed changes to letter-based invitations can increase uptake of NHS HCs. It also provides novel evidence on the effect of SMS reminders and pre-notification on NHS HC attendance

Detection and Monitoring of Microparticles Under Skin by Optical Coherence Tomography as an Approach to Continuous Glucose Sensing Using Implanted Retroreflectors

We demonstrate the feasibility of using optical coherence tomography (OCT) to image and detect 2.8 ?m diameter microparticles (stationary and moving) on a highly-reflective gold surface both in clear media and under skin in vitro. The OCT intensity signal can clearly report the microparticle count, and the OCT response to the number of microparticles shows a good linearity. The detect ability of the intensity change (2.9%�5%) caused by an individual microparticle shows the high sensitivity of monitoring multiple particles using OCT. An optical sensing method based on this feasibility study is described for continuously measuring blood sugar levels in the subcutaneous tissue, and a molecular recognition unit is designed using competitive binding to modulate the number of bound microparticles as a function of glucose concentration. With further development, an ultra-small, implantable sensor might provide high specificity and sensitivity for long-term continuous monitoring of blood glucose concentration

Clinical effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: the CoBalT randomised controlled trial

Background: Only one-third of patients with depression respond fully to treatment with antidepressant medication. However, there is little robust evidence to guide the management of those whose symptoms are 'treatment resistant'.&lt;p&gt;&lt;/p&gt; Objective: The CoBalT trial examined the clinical effectiveness and cost-effectiveness of cognitive behavioural therapy (CBT) as an adjunct to usual care (including pharmacotherapy) for primary care patients with treatment-resistant depression (TRD) compared with usual care alone.&lt;p&gt;&lt;/p&gt; Design: Pragmatic, multicentre individually randomised controlled trial with follow-up at 3, 6, 9 and 12 months. A subset took part in a qualitative study investigating views and experiences of CBT, reasons for completing/not completing therapy, and usual care for TRD.&lt;p&gt;&lt;/p&gt; Setting: General practices in Bristol, Exeter and Glasgow, and surrounding areas.&lt;p&gt;&lt;/p&gt; Participants: Patients aged 18-75 years who had TRD [on antidepressants for 6 weeks, had adhered to medication, Beck Depression Inventory, 2nd version (BDI-II) score of 14 and fulfilled the International Classification of Diseases and Related Health Problems, Tenth edition criteria for depression]. Individuals were excluded who (1) had bipolar disorder/psychosis or major alcohol/substance abuse problems; (2) were unable to complete the questionnaires; or (3) were pregnant, as were those currently receiving CBT/other psychotherapy/secondary care for depression, or who had received CBT in the past 3 years.&lt;p&gt;&lt;/p&gt; Interventions: Participants were randomised, using a computer-generated code, to usual care or CBT (12-18 sessions) in addition to usual care.&lt;p&gt;&lt;/p&gt; Main outcome measures: The primary outcome was 'response', defined as 50% reduction in depressive symptoms (BDI-II score) at 6 months compared with baseline. Secondary outcomes included BDI-II score as a continuous variable, remission of symptoms (BDI-II score of &lt; 10), quality of life, anxiety and antidepressant use at 6 and 12 months. Data on health and social care use, personal costs, and time off work were collected at 6 and 12 months. Costs from these three perspectives were reported using a cost-consequence analysis. A cost-utility analysis compared health and social care costs with quality adjusted life-years.&lt;p&gt;&lt;/p&gt; Results: A total of 469 patients were randomised (intervention: n = 234; usual care: n = 235), with 422 participants (90%) and 396 (84%) followed up at 6 and 12 months. Ninety-five participants (46.1%) in the intervention group met criteria for 'response' at 6 months compared with 46 (21.6%) in the usual-care group {odds ratio [OR] 3.26 [95% confidence interval (CI) 2.10 to 5.06], p &lt; 0.001}. In repeated measures analyses using data from 6 and 12 months, the OR for 'response' was 2.89 (95% CI 2.03 to 4.10, p &lt; 0.001) and for a secondary 'remission' outcome (BDI-II score of &lt; 10) 2.74 (95% CI 1.82 to 4.13, p &lt; 0.001). The mean cost of CBT per participant was £910, the incremental health and social care cost £850, the incremental QALY gain 0.057 and incremental cost-effectiveness ratio £14,911. Forty participants were interviewed. Patients described CBT as challenging but helping them to manage their depression; listed social, emotional and practical reasons for not completing treatment; and described usual care as mainly taking medication.&lt;p&gt;&lt;/p&gt; Conclusions: Among patients who have not responded to antidepressants, augmenting usual care with CBT is effective in reducing depressive symptoms, and these effects, including outcomes reflecting remission, are maintained over 12 months. The intervention was cost-effective based on the National Institute for Health and Care Excellence threshold. Patients may experience CBT as difficult but effective. Further research should evaluate long-term effectiveness, as this would have major implications for the recommended treatment of depression.&lt;p&gt;&lt;/p&gt

Helium beam shadowing for high spatial resolution patterning of antibodies on microstructured diagnostic surfaces

We have developed a technique for the high-resolution, self-aligning, and high-throughput patterning of antibody binding functionality on surfaces by selectively changing the reactivity of protein-coated surfaces in specific regions of a workpiece with a beam of energetic helium particles. The exposed areas are passivated with bovine serum albumin (BSA) and no longer bind the antigen. We demonstrate that patterns can be formed (1) by using a stencil mask with etched openings that forms a patterned exposure, or (2) by using angled exposure to cast shadows of existing raised microstructures on the surface to form self-aligned patterns. We demonstrate the efficacy of this process through the patterning of anti-lysozyme, anti-Norwalk virus, and anti-Escherichia coli antibodies and the subsequent detection of each of their targets by the enzyme-mediated formation of colored or silver deposits, and also by binding of gold nanoparticles. The process allows for the patterning of three-dimensional structures by inclining the sample relative to the beam so that the shadowed regions remain unaltered. We demonstrate that the resolution of the patterning process is of the order of hundreds of nanometers, and that the approach is well-suited for high throughput patterning

Public attitudes towards the use of novel technologies in their future healthcare: a UK survey

Background: Innovation in healthcare technologies can result in more convenient and effective treatment that is less costly, but a persistent challenge to widespread adoption in health and social care is end user acceptability. The purpose of this study was to capture UK public opinions and attitudes to novel healthcare technologies (NHTs), and to better understand the factors that contribute to acceptance and future use. Methods: An online survey was distributed to the UK public between April and May 2020. Respondents received brief information about four novel healthcare technologies (NHTs) in development: a laser-based tool for early diagnosis of osteoarthritis, a virtual reality tool to support diabetes self-management, a non-invasive continuous glucose monitor using microwave signals, a mobile app for patient reported monitoring of rheumatoid arthritis. They were queried on their general familiarity and attitudes to technology, and their willingness to accept each NHT in their future care. Responses were analysed using summary statistics and content analysis. Results: Knowledge about NHTs was diverse, with respondents being more aware about the health applications of mobile apps (66%), followed by laser-based technology (63.8%), microwave signalling (28%), and virtual reality (18.3%). Increasing age and the presence of a self-reported medical condition favoured acceptability for some NHTs, whereas self-reported understanding of how the NHT works resulted in elevated acceptance scores across all NHTs presented. Common contributors to hesitancy were safety and risks from use. Respondents wanted more information and evidence to help inform their decisions, ideally provided verbally by a general practitioner or health professional. Other concerns, such as privacy, were NHT-specific but equally important in decision-making. Conclusions: Early insight into the knowledge and preconceptions of the public about NHTs in development can assist their design and prospectively mitigate obstacles to acceptance and adoption

Soil respiratory quotient determined via barometric process separation combined with nitrogen-15 labeling

The barometric process separation (BaPS) and ¹⁵N dilution techniques were used to determine gross nitrification rates on the same soil cores from an old grassland soil. The BaPS-technique separates the O₂ consumption into that from nitrification and that from soil organic matter (SOM) respiration. The most sensitive parameter for the calculations via the BaPS technique is the respiratory quotient (RQ = ∆CO₂/∆O₂) for SOM turnover (RQSOM). Combining both methods (BaPS–¹⁵N ) allowed the determination of the RQSOM. The RQ value determined in such a way is adjusted for the influence of nitrification and denitrification, which are both characterized by totally different RQ values. The results for the grassland soil showed that 6 to 10% of O₂ was consumed by nitrification when incubated at 20°C and 0.49 g H₂O g⁻¹ soil. A set of BaPS measurements with the same soil at various temperature and moisture contents showed that up to 49% of the total O₂ consumption was due to nitrification. The calculated RQSOM values via the BaPS–¹⁵N technique presented here are more closely associated with the overall SOM turnover than the usual net RQ reported in the literature. Furthermore, the RQSOM value provides an overall indication of the decomposability and chemical characteristics of the respired organic material. Hence, it has the potential to serve as a single state index for SOM quality and therefore be a useful index for SOM turnover models based on substrate quality

Physical activity as a treatment for depression: the TREAD randomised trial protocol

Depression is one of the most common reasons for consulting a General Practitioner (GP) within the UK. Whilst antidepressants have been shown to be clinically effective, many patients and healthcare professionals would like to access other forms of treatment as an alternative or adjunct to drug therapy for depression. A recent systematic review presented some evidence that physical activity could offer one such option, although further investigation is needed to test its effectiveness within the context of the National Health Service.The aim of this paper is to describe the protocol for a randomised, controlled trial (RCT) designed to evaluate an intervention developed to increase physical activity as a treatment for depression within primary care

A simple spreadsheet-based, MIAME-supportive format for microarray data: MAGE-TAB

BACKGROUND: Sharing of microarray data within the research community has been greatly facilitated by the development of the disclosure and communication standards MIAME and MAGE-ML by the MGED Society. However, the complexity of the MAGE-ML format has made its use impractical for laboratories lacking dedicated bioinformatics support. RESULTS: We propose a simple tab-delimited, spreadsheet-based format, MAGE-TAB, which will become a part of the MAGE microarray data standard and can be used for annotating and communicating microarray data in a MIAME compliant fashion. CONCLUSION: MAGE-TAB will enable laboratories without bioinformatics experience or support to manage, exchange and submit well-annotated microarray data in a standard format using a spreadsheet. The MAGE-TAB format is self-contained, and does not require an understanding of MAGE-ML or XML

DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency.

During genome replication, polymerase epsilon (Pol ε) acts as the major leading-strand DNA polymerase. Here we report the identification of biallelic mutations in POLE, encoding the Pol ε catalytic subunit POLE1, in 15 individuals from 12 families. Phenotypically, these individuals had clinical features closely resembling IMAGe syndrome (intrauterine growth restriction [IUGR], metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary anomalies in males), a disorder previously associated with gain-of-function mutations in CDKN1C. POLE1-deficient individuals also exhibited distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency. All subjects shared the same intronic variant (c.1686+32C>G) as part of a common haplotype, in combination with different loss-of-function variants in trans. The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins

A high resolution record of multiple diagenetic events: Ultraviolet laser microprobe Ar/Ar analysis of zoned K-feldspar overgrowths

High spatial resolution UV laser Ar/Ar analyses were performed in situ oil K-feldspar overgrowths from sandstone hosted Pb-Zn bodies from central Sweden. Two different populations of ages were detected-Precambrian-Cambrian (528 +/- 10 to 567 +/- 8 Ma) and late Silurian (403 +/- 6 to 453 +/- 8 Ma). These were both detected in single pore spaces, with the older population adjacent to the detrital feldspar whilst the younger population was always distal to the detrital grain. This younging of authigenic K-feldspar ages with distance from the detrital grain margin is discussed in terms of disturbance to the argon system within an authigenic overgrowth that is of a single age: (a) the overgrowths are Precambrian-Cambrian in age and the late Silurian population might be an artefact of argon-loss due to partial resetting, (b) the overgrowths are late Silurian and the Precambrian-Cambrian population might have resulted from excess argon uptake, and (c) the overgrowths are late Silurian but the Precambrian-Cambrian population is an experimental artefact arising from the analysis of overlapping detrital/authigenic feldspars. Diffusion modelling shows that the partial resetting scenario is a very unlikely cause for the observed age variation because it requires a very particular arrangement of sub-grain sizes. Excess argon was not detected in either the K-feldspar or quartz. The data are best interpreted as the ages of two discrete diagenetic events-an early burial diagenesis and a later tectonically induced fluid flow event relating to the collapse of the Caledonian orogen. Further, the use of Ar-38(Cl)/Ar-39(K) as a proxy for Cl/K ratio highlights the physical boundaries between feldspar populations, where all other petrographic, SEM and CL analyses have failed to do so. This study shows that high spatial resolution UV laserprobe Ar/Ar analysis is a powerful tool for extracting age information from complex hydrothermal minerals as a means to investigating fluid flow events