Designing and Undertaking a Health Economics Study of Digital Health Interventions.

This paper introduces and discusses key issues in the economic evaluation of digital health interventions. The purpose is to stimulate debate so that existing economic techniques may be refined or new methods developed. The paper does not seek to provide definitive guidance on appropriate methods of economic analysis for digital health interventions. This paper describes existing guides and analytic frameworks that have been suggested for the economic evaluation of healthcare interventions. Using selected examples of digital health interventions, it assesses how well existing guides and frameworks align to digital health interventions. It shows that digital health interventions may be best characterized as complex interventions in complex systems. Key features of complexity relate to intervention complexity, outcome complexity, and causal pathway complexity, with much of this driven by iterative intervention development over time and uncertainty regarding likely reach of the interventions among the relevant population. These characteristics imply that more-complex methods of economic evaluation are likely to be better able to capture fully the impact of the intervention on costs and benefits over the appropriate time horizon. This complexity includes wider measurement of costs and benefits, and a modeling framework that is able to capture dynamic interactions among the intervention, the population of interest, and the environment. The authors recommend that future research should develop and apply more-flexible modeling techniques to allow better prediction of the interdependency between interventions and important environmental influences.This paper is one of the outputs of two workshops, one supported by the Medical Research Council (MRC)/National Institute for Health Research (NIHR) Methodology Research Programme (PI Susan Michie) and the Robert Wood Johnson Foundation (PI Kevin Patrick), and the other by the National Science Foundation (PI Donna Spruitj-Metz, proposal # 1539846). The Health Economics Research Unit is funded in part by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Elsevier

Titan Science with the James Webb Space Telescope (JWST)

The James Webb Space Telescope (JWST), scheduled for launch in 2018, is the successor to the Hubble Space Telescope (HST) but with a significantly larger aperture (6.5 m) and advanced instrumentation focusing on infrared science (0.6-28.0 $\mu$m ). In this paper we examine the potential for scientific investigation of Titan using JWST, primarily with three of the four instruments: NIRSpec, NIRCam and MIRI, noting that science with NIRISS will be complementary. Five core scientific themes are identified: (i) surface (ii) tropospheric clouds (iii) tropospheric gases (iv) stratospheric composition and (v) stratospheric hazes. We discuss each theme in depth, including the scientific purpose, capabilities and limitations of the instrument suite, and suggested observing schemes. We pay particular attention to saturation, which is a problem for all three instruments, but may be alleviated for NIRCam through use of selecting small sub-arrays of the detectors - sufficient to encompass Titan, but with significantly faster read-out times. We find that JWST has very significant potential for advancing Titan science, with a spectral resolution exceeding the Cassini instrument suite at near-infrared wavelengths, and a spatial resolution exceeding HST at the same wavelengths. In particular, JWST will be valuable for time-domain monitoring of Titan, given a five to ten year expected lifetime for the observatory, for example monitoring the seasonal appearance of clouds. JWST observations in the post-Cassini period will complement those of other large facilities such as HST, ALMA, SOFIA and next-generation ground-based telescopes (TMT, GMT, EELT).Comment: 50 pages, including 22 figures and 2 table

Youth chances: integrated report

This document provides an overview of the key findings from this five-year ground-breaking research project about the experiences of lesbian, gay, bisexual, trans and questioning (LGBTQ) 16-25year olds in England funded by the Big Lottery Fund and conducted by METRO Charity in collaboration with Ergo Consulting and the University of Greenwich. Methods: The project surveyed 7,126 young people aged 16-25. Of these 6,514 were LGBTQ young people. 612 were heterosexual non-trans young people and 956 were trans young people. 29 commissioners of services for young people and 52 relevant service providers across England were also surveyed. Findings: Show high levels of discrimination, abuse and mental health issues that young LGBTQ people face which indicate a need for more to be done to improve the lives of LGBTQ young people. Sections of the report are: 1. Being different Over half of LGBQ respondents (53%) knew they were LGBQ by the age of 13. Over half of trans respondents (58%) knew they were trans by the same age. When coming out as LGBQ or trans, over four fifths of LGBQ respondents (81%) and nearly two thirds of trans respondents (62%) told a friend first. Over a quarter of LGBQ young people (29%) have not told their mother, nearly a half (45%) have not told their father, and 5% have not told anybody. Approximately half of trans respondents have not told parents or siblings that they are trans and 28% have not told anybody. Young people tell us that they most want emotional support to help them when they are coming out but most are not getting it. The second most important thing to them is to meet other LGBTQ people and again over half of them did not get this opportunity. 2. Participation LGBTQ young people are twice as likely not to feel accepted in the area where they currently live, compared to heterosexual non-trans young people. 59% of LGBTQ young people that would be interested in joining a religious organisation have stopped or reduced their involvement owing to their sexuality or gender identity. Over a third of LGBTQ young people (34%) are not able to be open about their sexuality or gender identity at a sports club they are involved in. 3. Staying safe 73% of the LGBTQ sample agreed that discrimination against LGB people is still common and 90% of the LGBTQ sample agreed that discrimination against trans people is still common. About three quarters of LGBTQ young people (74%) have experienced name calling, nearly a half (45%) have experienced harassment or threats and intimidation and almost a quarter (23%) have experienced physical assault. 88% of LGBTQ young people do not report incidents to the police and when cases are reported only 10% lead to a conviction. 29% of LGBTQ respondents reported domestic or familial abuse, compared to 25% of the heterosexual non trans group. Over a third (36%) of LGBTQ respondents cited their sexuality or gender identity as at least a contributing factor in the abuse. Almost one in five (18%) LGBTQ young people have experienced some form of sexual abuse, compared with one in ten (11%) of non-trans heterosexuals in our sample. Most LGBTQ respondents who have experienced sexual abuse (79%) have not received any help or support. Nearly one in ten LGBTQ young people report that they have had to leave home for reasons relating to their sexuality or gender identity. 4. Enjoying and achieving Nearly half of LGBTQ young people (49%) reported that their time at school was affected by discrimination or fear of discrimination. Consequences reported included missing lessons, achieving lower grades, feeling isolated and left out and having to move schools are all reported. 61% reported name calling because they were LGBTQ or people thought they were. This figure includes the experiences of heterosexual non-trans respondents: it is an issue for all young people. About one in five LGBTQ young people experience physical attack at school on account of their sexual identity or gender identity. The majority do not report this and only a small proportion of those who do experience resolution. For some reporting the abuse means that it gets worse. Around two thirds of LGBTQ young people say they learn a lot about relationships and safer sex between a man and a woman, compared to less than 5% who say they learn a lot about same sex relationships and safer sex. 89% of LGBTQ young people report learning nothing about bisexuality issues and 94% report learning nothing about transgender issues. Only 25% of LGBTQ young people report that they learned anything at school about safer sex for a male couple

Prelimbic and infralimbic cortical regions differentially encode cocaine-associated stimuli and cocaine-seeking before and following abstinence

Cocaine stimuli often trigger relapse of drug-taking, even following periods of prolonged abstinence. Here, electrophysiological recordings were made in rats (n = 29) to determine how neurons in the prelimbic (PrL) or infralimbic (IL) regions of the medial prefrontal cortex (mPFC) encode cocaine-associated stimuli and cocaine-seeking, and whether this processing is differentially altered after 1 month of cocaine abstinence. After self-administration training, neurons (n=308) in the mPFC were recorded during a single test session conducted either the next day or 1 month later. Test sessions consisted of three phases during which (i) the tone–houselight stimulus previously paired with cocaine infusion during self-administration was randomly presented by the experimenter, (ii) rats responded on the lever previously associated with cocaine during extinction and (iii) the tone–houselight was presented randomly between cocaine-reinforced responding during resumption of cocaine self-administration. PrL neurons showed enhanced encoding of the cocaine stimulus and drug-seeking behavior (under extinction and self-administration) following 30 days of abstinence. In contrast, although IL neurons encoded cocaine cues and cocaine-seeking, there were no pronounced changes in IL responsiveness following 30 days’ abstinence. Importantly, cue-related changes do not represent a generalized stimulus-evoked discharge as PrL and IL neurons in control animals (n=4) exhibited negligible recruitment by the tone–houselight stimulus. The results support the view that, following abstinence, neural encoding in the PrL but not IL may play a key role in enhanced cocaine-seeking, particularly following re-exposure to cocaine-associated cues

The metastable Q 3Δ2^3\Delta_2 state of ThO: A new resource for the ACME electron EDM search

The best upper limit for the electron electric dipole moment was recently set by the ACME collaboration. This experiment measures an electron spin-precession in a cold beam of ThO molecules in their metastable $H~(^3\Delta_1)$ state. Improvement in the statistical and systematic uncertainties is possible with more efficient use of molecules from the source and better magnetometry in the experiment, respectively. Here, we report measurements of several relevant properties of the long-lived $Q~(^3\Delta_2)$ state of ThO, and show that this state is a very useful resource for both these purposes. The $Q$ state lifetime is long enough that its decay during the time of flight in the ACME beam experiment is negligible. The large electric dipole moment measured for the $Q$ state, giving rise to a large linear Stark shift, is ideal for an electrostatic lens that increases the fraction of molecules detected downstream. The measured magnetic moment of the $Q$ state is also large enough to be used as a sensitive co-magnetometer in ACME. Finally, we show that the $Q$ state has a large transition dipole moment to the $C~(^1\Pi_1)$ state, which allows for efficient population transfer between the ground state $X~(^1\Sigma^+)$ and the $Q$ state via $X-C-Q$ Stimulated Raman Adiabatic Passage (STIRAP). We demonstrate $90\,$% STIRAP transfer efficiency. In the course of these measurements, we also determine the magnetic moment of $C$ state, the $X\rightarrow C$ transition dipole moment, and branching ratios of decays from the $C$ state.Comment: 21 pages, 6 figures, 5 pages appendice

Flash glucose monitoring in young people with type 1 diabetes — a qualitative study of young people, parents and health professionals : ‘It makes life much easier’

Objectives: Flash glucose monitoring for patients with T1 diabetes avoids frequent painful finger-prick testing, thus potentially improving frequency of glucose self-monitoring. Our study aimed to explore experiences of young people using Freestyle Libre sensors and their parents, and to identify benefits and challenges to National Health Service (NHS) staff of its adoption in their care provision. Participants: Young people with T1 diabetes, their parents and healthcare professionals were interviewed between February and December 2021. Participants were recruited via social media and through NHS diabetes clinic staff. Design: Semistructured interviews were conducted online and analysed using thematic methods. Staff themes were mapped onto normalisation process theory (NPT) constructs. Results: Thirty-four participants were interviewed: 10 young people, 14 parents and 10 healthcare professionals. Young people reported that life was much easier since changing to flash glucose monitoring, increasing confidence and independence to manage their condition. Parents’ quality of life improved and they appreciated access to real-time data. Using the NPT concepts to understand how technology was integrated into routine care proved useful; health professionals were very enthusiastic about flash glucose monitoring and coped with the extra data load to facilitate more tailored patient support within and between clinic visits. Conclusion: This technology empowers young people and their parents to understand their diabetes adherence more completely; to feel more confident about adjusting their own care between clinic appointments; and provides an improved interactive experience in clinic. Healthcare teams appear committed to delivering improving technologies, acknowledging the challenge for them to assimilate new information required to provide expert advice

Azithromycin Mass Treatment for Trachoma Control: Risk Factors for Non-Participation of Children in Two Treatment Rounds

The World Health Organization advocates at least three mass drug administrations (MDAs) with antibiotics when the prevalence of follicular trachoma (TF) is greater than 10% in children under age ten. Full child participation is necessary for maximizing the impact of trachoma control programs. The present paper identifies guardian, household, and program risk factors for households with a child who never participated in two annual rounds of MDAs with azithromycin. In comparison to households with full child participation, guardians with at least one child who never participated had a higher burden of familial responsibility, as represented by reporting ill family members, more children, and were younger in age. In addition, guardians of persistent non-participants seemed less well connected in the community, in terms of reliance on others and not knowing who their assigned community treatment assistants (CTAs) were. These guardians were assigned to CTAs who had a wide geographic dispersion of their assigned households. By developing programs with local groups to find and encourage participation in at-risk households, program managers may have the greatest impact on preventing persistent child non-participation. Increasing the number of distribution days and reducing CTAs' travel time may further prevent non-participation

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status