Does a monetary incentive improve the response to a postal questionnaire in a randomised controlled trial? : the MINT incentive study

Background: Sending a monetary incentive with postal questionnaires has been found to improve the proportion of responders, in research in non-healthcare settings. However, there is little research on use of incentives to improve follow-up rates in clinical trials, and existing studies are inconclusive. We conducted a randomised trial among participants in the Managing Injuries of the Neck Trial (MINT) to investigate the effects on the proportion of questionnaires returned and overall non-response of sending a £5 gift voucher with a follow-up questionnaire. Methods: Participants in MINT were randomised to receive either: (a) a £5 gift voucher (incentive group) or (b) no gift voucher (no incentive group), with their 4 month or 8 month follow-up questionnaire. We recorded, for each group, the number of questionnaires returned, the number returned without any chasing from the study office, the overall number of non-responders (after all chasing efforts by the study office), and the costs of following up each group. Results: 2144 participants were randomised, 1070 to the incentive group and 1074 to the no incentive group. The proportion of questionnaires returned (RR 1.10 (95% CI 1.05, 1.16)) and the proportion returned without chasing (RR 1.14 (95% CI 1.05, 1.24) were higher in the incentive group, and the overall non-response rate was lower (RR 0.68 (95% CI 0.53, 0.87)). Adjustment for injury severity and hospital of recruitment to MINT made no difference to these results, and there were no differences in results between the 4-month and 8-month follow up questionnaires. Analysis of costs suggested a cost of £67.29 per additional questionnaire returned. Conclusion: Monetary incentives may be an effective way to increase the proportion of postal questionnaires returned and minimise loss to follow-up in clinical trials

Elevated pulse pressure is associated with hemolysis, proteinuria and chronic kidney disease in sickle cell disease

A seeming paradox of sickle cell disease is that patients do not suffer from a high prevalence of systemic hypertension in spite of endothelial dysfunction, chronic inflammation and vasculopathy. However, some patients do develop systolic hypertension and increased pulse pressure, an increasingly recognized major cardiovascular risk factor in other populations. Hence, we hypothesized that pulse pressure, unlike other blood pressure parameters, is independently associated with markers of hemolytic anemia and cardiovascular risk in sickle cell disease. We analyzed the correlates of pulse pressure in patients (n 5 661) enrolled in a multicenter international sickle cell trial. Markers of hemolysis were analyzed as independent variables and as a previously validated hemolytic index that includes multiple variables. We found that pulse pressure, not systolic, diastolic or mean arterial pressure, independently correlated with high reticulocyte count (beta 5 2.37, p 5 0.02) and high hemolytic index (beta 5 1.53, p50.002) in patients with homozygous sickle cell disease in two multiple linear regression models which include the markers of hemolysis as independent variables or the hemolytic index, respectively. Pulse pressure was also independently associated with elevated serum creatinine (beta 5 3.21, p 5 0.02), and with proteinuria (beta 5 2.52, p 5 0.04). These results from the largest sickle cell disease cohort to date since the Cooperative Study of Sickle Cell Disease show that pulse pressure is independently associated with hemolysis, proteinuria and chronic kidney disease. We propose that high pulse pressure may be a risk factor for clinical complications of vascular dysfunction in sickle cell disease. Longitudinal and mechanistic studies should be conducted to confirm these hypotheses

Managing Injuries of the Neck Trial (MINT) : design of a randomised controlled trial of treatments for whiplash associated disorders

Background: A substantial proportion of patients with whiplash injuries develop chronic symptoms. However, the best treatment of acute injuries to prevent long-term problems is uncertain. A stepped care treatment pathway has been proposed, in which patients are given advice and education at their initial visit to the emergency department (ED), followed by review at three weeks and physiotherapy for those with persisting symptoms. MINT is a two-stage randomised controlled trial to evaluate two components of such a pathway: 1. use of The Whiplash Book versus usual advice when patients first attend the emergency department; 2. referral to physiotherapy versus reinforcement of advice for patients with continuing symptoms at three weeks. Methods: Evaluation of the Whiplash Book versus usual advice uses a cluster randomised design in emergency departments of eight NHS Trusts. Eligible patients are identified by clinicians in participating emergency departments and are sent a study questionnaire within a week of their ED attendance. Three thousand participants will be included. Patients with persisting symptoms three weeks after their ED attendance are eligible to join an individually randomised study of physiotherapy versus reinforcement of the advice given in ED. Six hundred participants will be randomised. Follow-up is at 4, 8 and 12 months after their ED attendance. Primary outcome is the Neck Disability Index (NDI), and secondary outcomes include quality of life and time to return to work and normal activities. An economic evaluation is being carried out. Conclusion: This paper describes the protocol and operational aspects of a complex intervention trial based in NHS emergency and physiotherapy departments, evaluating two components of a stepped-care approach to the treatment of whiplash injuries. The trial uses two randomisations, with the first stage being cluster randomised and the second individually randomised

Risk-Driven Design Processes: Balancing Efficiency with Resilience in Product Design

Current design methods and approaches focus on increasing the efficiency of the product design system by, for example, eliminating waste and focusing on value creation. However, continuing failures in the development of complex, large scale products and systems point towards weaknesses in the existing approaches. We argue that product development organizations are hindered by the many uncertainties that are inherent in the process. Common management heuristics ignore uncertainty and thus overly simplify the decision making process. Creating transparency regarding uncertainties and the associated risks (i.e. effect of uncertainties on design objectives) is not seen as an explicit priority. Consequently organizations are unable to balance risk and return in their development choices. Product development processes do not emphasize reduction of risks, particularly those risks that are apparent early in the process. In addition, the resilience of the PD system, i.e. its ability to deliver on-target results under uncertainty, is not deliberately designed to match the level of residual uncertainty. This chapter introduces the notion of Risk-Driven Design and its four principles of 1. Creating transparency regarding design risks; 2. Risk-driven decision making; 3. Minimizing uncertainty; and 4. Creating resilience.Massachusetts Institute of Technology. Lean Advancement InitiativeCenter for Clean Water and Clean Energy at MIT and KFUP

Spectral compression of single photons

Photons are critical to quantum technologies since they can be used for virtually all quantum information tasks: in quantum metrology, as the information carrier in photonic quantum computation, as a mediator in hybrid systems, and to establish long distance networks. The physical characteristics of photons in these applications differ drastically; spectral bandwidths span 12 orders of magnitude from 50 THz for quantum-optical coherence tomography to 50 Hz for certain quantum memories. Combining these technologies requires coherent interfaces that reversibly map centre frequencies and bandwidths of photons to avoid excessive loss. Here we demonstrate bandwidth compression of single photons by a factor 40 and tunability over a range 70 times that bandwidth via sum-frequency generation with chirped laser pulses. This constitutes a time-to-frequency interface for light capable of converting time-bin to colour entanglement and enables ultrafast timing measurements. It is a step toward arbitrary waveform generation for single and entangled photons.Comment: 6 pages (4 figures) + 6 pages (3 figures

When Did HIV Incidence Peak in Harare, Zimbabwe? Back-Calculation from Mortality Statistics

HIV prevalence has recently begun to decline in Zimbabwe, a result of both high levels of AIDS mortality and a reduction in incident infections. An important component in understanding the dynamics in HIV prevalence is knowledge of past trends in incidence, such as when incidence peaked and at what level. However, empirical measurements of incidence over an extended time period are not available from Zimbabwe or elsewhere in sub-Saharan Africa. Using mortality data, we use a back-calculation technique to reconstruct historic trends in incidence. From AIDS mortality data, extracted from death registration in Harare, together with an estimate of survival post-infection, HIV incidence trends were reconstructed that would give rise to the observed patterns of AIDS mortality. Models were fitted assuming three parametric forms of the incidence curve and under nine different assumptions regarding combinations of trends in non-AIDS mortality and patterns of survival post-infection with HIV. HIV prevalence was forward-projected from the fitted incidence and mortality curves. Models that constrained the incidence pattern to a cubic spline function were flexible and produced well-fitting, realistic patterns of incidence. In models assuming constant levels of non-AIDS mortality, annual incidence peaked between 4 and 5% between 1988 and 1990. Under other assumptions the peak level ranged from 3 to 8% per annum. However, scenarios assuming increasing levels of non-AIDS mortality resulted in implausibly low estimates of peak prevalence (11%), whereas models with decreasing underlying crude mortality could be consistent with the prevalence and mortality data. HIV incidence is most likely to have peaked in Harare between 1988 and 1990, which may have preceded the peak elsewhere in Zimbabwe. This finding, considered alongside the timing and location of HIV prevention activities, will give insight into the decline of HIV prevalence in Zimbabwe

An exploratory cluster randomised trial of a university halls of residence based social norms marketing campaign to reduce alcohol consumption among 1st year students

<p>Aims: This exploratory trial examines the feasibility of implementing a social norms marketing campaign to reduce student drinking in universities in Wales, and evaluating it using cluster randomised trial methodology.</p> <p>Methods: Fifty residence halls in 4 universities in Wales were randomly assigned to intervention or control arms. Web and paper surveys were distributed to students within these halls (n = 3800), assessing exposure/contamination, recall of and evaluative responses to intervention messages, perceived drinking norms and personal drinking behaviour. Measures included the Drinking Norms Rating Form, the Daily Drinking Questionnaire and AUDIT-C.</p> <p>Results: A response rate of 15% (n = 554) was achieved, varying substantially between sites. Intervention posters were seen by 80% and 43% of students in intervention and control halls respectively, with most remaining materials seen by a minority in both groups. Intervention messages were rated as credible and relevant by little more than half of students, though fewer felt they would influence their behaviour, with lighter drinkers more likely to perceive messages as credible. No differences in perceived norms were observed between intervention and control groups. Students reporting having seen intervention materials reported lower descriptive and injunctive norms than those who did not.</p> <p>Conclusions: Attention is needed to enhancing exposure, credibility and perceived relevance of intervention messages, particularly among heavier drinkers, before definitive evaluation can be recommended. A definitive evaluation would need to consider how it would achieve sufficient response rates, whilst hall-level cluster randomisation appears subject to a significant degree of contamination.</p&gt

The Effectiveness of Alcohol Screening and Brief Intervention in Emergency Departments: A Multicentre Pragmatic Cluster Randomized Controlled Trial

BACKGROUND: Alcohol misuse is common in people attending emergency departments (EDs) and there is some evidence of efficacy of alcohol screening and brief interventions (SBI). This study investigated the effectiveness of SBI approaches of different intensities delivered by ED staff in nine typical EDs in England: the SIPS ED trial. METHODS AND FINDINGS: Pragmatic multicentre cluster randomized controlled trial of SBI for hazardous and harmful drinkers presenting to ED. Nine EDs were randomized to three conditions: a patient information leaflet (PIL), 5 minutes of brief advice (BA), and referral to an alcohol health worker who provided 20 minutes of brief lifestyle counseling (BLC). The primary outcome measure was the Alcohol Use Disorders Identification Test (AUDIT) status at 6 months. Of 5899 patients aged 18 or more presenting to EDs, 3737 (63·3%) were eligible to participate and 1497 (40·1%) screened positive for hazardous or harmful drinking, of whom 1204 (80·4%) gave consent to participate in the trial. Follow up rates were 72% (n?=?863) at six, and 67% (n?=?810) at 12 months. There was no evidence of any differences between intervention conditions for AUDIT status or any other outcome measures at months 6 or 12 in an intention to treat analysis. At month 6, compared to the PIL group, the odds ratio of being AUDIT negative for brief advice was 1·103 (95% CI 0·328 to 3·715). The odds ratio comparing BLC to PIL was 1·247 (95% CI 0·315 to 4·939). A per protocol analysis confirmed these findings. CONCLUSIONS: SBI is difficult to implement in typical EDs. The results do not support widespread implementation of alcohol SBI in ED beyond screening followed by simple clinical feedback and alcohol information, which is likely to be easier and less expensive to implement than more complex interventions

Spectral determination of the colour and vertical structure of dark spots in Neptune's atmosphere

Previous observations of dark vortices in Neptune's atmosphere, such as Voyager-2's Great Dark Spot, have been made in only a few, broad-wavelength channels, which has hampered efforts to pinpoint their pressure level and what makes them dark. Here, we present Very Large Telescope (Chile) MUSE spectrometer observations of Hubble Space Telescope's NDS-2018 dark spot, made in 2019. These medium-resolution 475 - 933 nm reflection spectra allow us to show that dark spots are caused by a darkening at short wavelengths (< 700 nm) of a deep ~5-bar aerosol layer, which we suggest is the H$_2$S condensation layer. A deep bright spot, named DBS-2019, is also visible on the edge of NDS-2018, whose spectral signature is consistent with a brightening of the same 5-bar layer at longer wavelengths (> 700 nm). This bright feature is much deeper than previously studied dark spot companion clouds and may be connected with the circulation that generates and sustains such spots.Comment: 1 table. 3 figures. Nature Astronomy (2023

Spectral determination of the colour and vertical structure of dark spots in Neptune’s atmosphere

Previous observations of dark vortices in Neptune’s atmosphere, such as Voyager 2’s Great Dark Spot (1989), have been made in only a few broad-wavelength channels, hampering efforts to determine these vortices’ pressure levels and darkening processes. We analyse spectroscopic observations of a dark spot on Neptune identified by the Hubble Space Telescope as NDS-2018; the spectral observations were made in 2019 by the Multi Unit Spectroscopic Explorer (MUSE) of the Very Large Telescope (Chile). The MUSE medium-resolution 475–933 nm reflection spectra allow us to show that dark spots are caused by darkening at short wavelengths (700 nm). This bright feature is much deeper than previously studied dark-spot companion clouds and may be connected with the circulation that generates and sustains such spots