Exploring the incidence of inadequate response to antidepressants in the primary care of depression.

Data from the UK suggests 13-55 % of depression patients experience some level of treatment resistance. However, little is known about how physicians manage inadequate response to antidepressants in primary care. This study aimed to explore the incidence of inadequate response to antidepressants in UK primary care. One-hundred-eighty-four medication-free patients with low mood initiated antidepressant treatment and monitored severity of depression symptoms, using the QIDS-SR16, for 48 weeks. Medication changes, visits to healthcare providers, and health-related quality of life were also recorded. Patients were classified into one of four response types based on their QIDS scores at three study timepoints: persistent inadequate responders (<50 % reduction in baseline QIDS at all timepoints), successful responders (≥50 % reduction in baseline QIDS at all timepoints), slow responders (≥50 % reduction in QIDS at week 48, despite earlier inadequate responses), and relapse (initial ≥50 % reduction in baseline QIDS, but inadequate response by week 48). Forty-eight weeks after initiating treatment 47 % of patients continued to experience symptoms of depression (QIDS >5), and 20 % of patients had a persistent inadequate response. Regardless of treatment response, 96 % (n = 176) of patients did not visit their primary care physician over the 40-week follow-up period. These results suggest that despite receiving treatment, a considerable proportion of patients with low mood remain unwell and fail to recover. Monitoring depression symptoms remotely can enable physicians to identify inadequate responders, allowing patients to be reassessed or referred to secondary services, likely improving patients' quality of life and reducing the socioeconomic impacts of chronic mental illness.

When a test is more than just a test: Findings from patient interviews and survey in the trial of a technology to measure antidepressant medication response (the PReDicT Trial).

BACKGROUND: A RCT of a novel intervention to detect antidepressant medication response (the PReDicT Test) took place in five European countries, accompanied by a nested study of its acceptability and implementation presented here. The RCT results indicated no effect of the intervention on depression at 8 weeks (primary outcome), although effects on anxiety at 8 weeks and functioning at 24 weeks were found. METHODS: The nested study used mixed methods. The aim was to explore patient experiences of the Test including acceptability and implementation, to inform its use within care. A bespoke survey was completed by trial participants in five countries (n = 778) at week 8. Semi-structured interviews were carried out in two countries soon after week 8 (UK n = 22, Germany n = 20). Quantitative data was analysed descriptively; for qualitative data, thematic analysis was carried out using a framework approach. Results of the two datasets were interrogated together. OUTCOMES: Survey results showed the intervention was well received, with a majority of participants indicating they would use it again, and it gave them helpful extra information; a small minority indicated the Test made them feel worse. Qualitative data showed the Test had unexpected properties, including: instigating a process of reflection, giving participants feedback on progress and new understanding about their illness, and making participants feel supported and more engaged in treatment. INTERPRETATION: The qualitative and quantitative results are generally consistent. The Test's unexpected properties may explain why the RCT showed little effect, as properties were experienced across both trial arms. Beyond the RCT, the qualitative data sheds light on measurement reactivity, i.e., how measurements of depression can impact patients.

Using a Novel Gameplay Intervention to Target Intrusive Memories After Work-Related Trauma: Iterative Qualitative Analysis of Intensive Care Unit Staff Experiences.

BACKGROUND: Many intensive care unit (ICU) staff experience intrusive memories following work-related traumatic events, which can lead to long-term mental health outcomes and impact work functioning. There is a need for interventions that target intrusive memories in this population; however, factors such as mental health stigma and difficulty in fitting interventions into busy schedules can pose barriers. The Brief Gameplay Intervention For National Health Service Intensive Care Unit Staff Affected By COVID-19 Trauma (GAINS) study tested a brief, digital imagery-competing task intervention (including computer gameplay) with the aim of reducing the recurrence of intrusive memories, which holds promise for overcoming some of these barriers. OBJECTIVE: This substudy aims to explore barriers and facilitators to the uptake and practical use of the intervention by ICU staff, along with its acceptability, and iteratively explore the impact of intervention optimizations to further refine the intervention. METHODS: The GAINS study is a randomized controlled trial comparing access to a brief digital imagery-competing task intervention for 4 weeks with usual care followed by delayed access to the intervention. The participants were ICU staff who worked during the COVID-19 pandemic and experienced intrusive memories. All participants were sent a questionnaire at 4 weeks to gather data about intervention acceptability. Nested within the randomized controlled trial, a subset of 16 participants was interviewed, and data were analyzed using thematic analysis drawing from a framework approach. RESULTS: Both quantitative and qualitative data indicated high acceptability of the intervention. Intervention use data show that, on average, staff were able to target approximately 73% (3.64/4.88) of their intrusive memories and engaged with the Tetris component for the full 20 minutes per session. Overall, on the acceptability questionnaire, staff found the intervention easy to use, helpful, and highly acceptable. The interviews generated four themes: approach to the intervention, positives of the intervention, negatives of the intervention, and improvements and optimizations. Findings highlighted barriers that ICU staff experienced: stigma, feeling weak for seeking help, not wanting colleagues to know they were struggling, and skepticism. However, they provided suggestions on how barriers could be overcome and discussed the advantages of the intervention when compared with other treatments. Although participants described many positive aspects of the intervention, such as being easy to use, enjoyable, and leading to a reduction in the frequency or intensity of intrusive memories, they also raised practical issues for implementation. CONCLUSIONS: The intervention has the potential to overcome stigma and reduce the frequency of intrusive memories after traumatic events among ICU staff. Further refinement is needed to improve the adoption and reach of this intervention. A limitation is that we could not interview the National Health Service staff who were unable or unwilling to take part in the trial.

Acceptability and utility of digital well-being and mental health support for university students: A pilot study.

AIM: To assess the acceptability and explore the utility of a novel digital platform designed as a student-facing well-being and mental health support. METHODS: An adapted version of i-spero® was piloted as a student-facing well-being support and as part of routine university-based mental health care. In both pathways, student participants completed baseline demographics and brief validated measures of well-being and mental health. Weekly measures of anxiety (GAD-7) and depression (PHQ-9) and a Week 8 Experience Survey were also scheduled. Integrated mixed methods analysis was used to assess acceptability and explore the utility of these platforms. RESULTS: Students in the well-being (n = 120) and care pathways (n = 121) were mostly female and between 19 and 22 years of age. Baseline screen positive rates for anxiety and depression were high in both the well-being (68%) and care pathways (80%). There was a substantial drop in adherence over Week 1 (50% well-being; 40% care) followed by minor attrition up to Week 8. Anxiety and depressive symptom levels improved from baseline in students who dropped out after Week 1 (p ≤ .06). The student experience was that i-spero® improved their emotional self-awareness, understanding of progress in care, and knowledge about when to seek help. Most students agreed (>75%) that i-spero® should form part of regular university student wellness support. CONCLUSIONS: Digital well-being and mental health support seems acceptable to university students; however, engagement and persistence are areas for further development. Such digital tools could make a positive contribution to an evidence-based stepped approach to student well-being and mental health support.

Reducing intrusive memories after trauma via an imagery-competing task intervention in COVID-19 intensive care staff: a randomised controlled trial.

Intrusive memories (IMs) after traumatic events can be distressing and disrupt mental health and functioning. We evaluated the impact of a brief remotely-delivered digital imagery-competing task intervention on the number of IMs for intensive care unit (ICU) staff who faced repeated trauma exposure during the COVID-19 pandemic using a two-arm, parallel-group, single-blind randomised controlled trial, with the comparator arm receiving delayed access to active treatment (crossover). Eligible participants worked clinically in a UK NHS ICU during the pandemic and had at least 3 IMs of work-related traumatic events in the week before recruitment. Participants were randomly assigned (1:1) to immediate (weeks 1-4) or delayed (weeks 5-8) intervention access. Sequential Bayesian analyses to optimise the intervention and increase trial efficiency are reported elsewhere [1]. The primary endpoint for the pre-specified frequentist analysis of the final study population compared the number of IMs experienced in week 4 between the immediate and delayed access arms. Secondary outcomes included clinical symptoms, work functioning and wellbeing. Safety was assessed throughout the trial by scheduled questions and free report. All analyses were undertaken on an intention-to-treat basis (86 randomised participants). There were significantly fewer intrusive memories during week 4 in the immediate (median = 1, IQR = 0-3, n = 43), compared to the comparator delayed arm (median = 10, IQR = 6-17, n = 43), IRR 0.31, 95% CI: 0.20-0.48, p < 0.001. After crossover, the delayed arm also showed a significant reduction in IMs at week 8 compared to week 4. There were convergent findings for symptoms of PTSD, insomnia and anxiety, work engagement and burnout, general functioning and quality of life. The intervention was found safe and acceptable to participants. All adverse events were unrelated to the study. Our study provides the first evidence of a benefit on reducing IMs, improving other clinical symptoms, work functioning and wellbeing, as well as safety of a brief remotely-delivered digital imagery-competing task intervention. An efficacy trial with an active control and longer follow-up is warranted. The trial is registered at ClinicalTrials.gov (NCT04992390).

Combining antidepressants and attention bias modification in primary health care (DEPTREAT): Protocol for a pragmatic randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent psychiatric condition associated with significant disability, mortality and economic burden. A large proportion of MDD patients are treated in primary health care in the local community. Attentional Bias Modification (ABM) training in combination with antidepressants could be an effective treatment. Here we test the hypothesis that adding an ABM procedure to regular treatment with antidepressants in primary health care will result in further improvement of symptoms compared to treatment with antidepressants alone (treatment as usual, TAU) and as compared to an active comparison condition. METHODS: A total of 246 patients with a diagnosis of MDD will be included in this study. The study is a three-armed pragmatic randomized controlled trial comparing the efficacy of ABM as add-on to treatment with antidepressants in primary care (ABM condition) compared to standard antidepressant treatment (TAU condition). In a third group participants will complete the same schedule of intermediate assessments as the ABM condition in addition to TAU, but no ABM, thus controlling for the non-training-specific aspects of the ABM condition (Antidepressant active comparison group). DISCUSSION: The clinical outcome of this study may help develop easily accessible, low-cost treatment of depression in primary health care. Moreover, the study aims to broaden our knowledge of optimal treatment for patients with a MDD by providing adjunct treatment to facilitate recovery and long-term gain.

Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention.

Intensive care unit (ICU) staff continue to face recurrent work-related traumatic events throughout the COVID-19 pandemic. Intrusive memories (IMs) of such traumatic events comprise sensory image-based memories. Harnessing research on preventing IMs with a novel behavioural intervention on the day of trauma, here we take critical next steps in developing this approach as a treatment for ICU staff who are already experiencing IMs days, weeks, or months post-trauma. To address the urgent need to develop novel mental health interventions, we used Bayesian statistical approaches to optimise a brief imagery-competing task intervention to reduce the number of IMs. We evaluated a digitised version of the intervention for remote, scalable delivery. We conducted a two-arm, parallel-group, randomised, adaptive Bayesian optimisation trial. Eligible participants worked clinically in a UK NHS ICU during the pandemic, experienced at least one work-related traumatic event, and at least three IMs in the week prior to recruitment. Participants were randomised to receive immediate or delayed (after 4 weeks) access to the intervention. Primary outcome was the number of IMs of trauma during week 4, controlling for baseline week. Analyses were conducted on an intention-to-treat basis as a between-group comparison. Prior to final analysis, sequential Bayesian analyses were conducted (n = 20, 23, 29, 37, 41, 45) to inform early stopping of the trial prior to the planned maximum recruitment (n = 150). Final analysis (n = 75) showed strong evidence for a positive treatment effect (Bayes factor, BF = 1.25 × 106): the immediate arm reported fewer IMs (median = 1, IQR = 0-3) than the delayed arm (median = 10, IQR = 6-16.5). With further digital enhancements, the intervention (n = 28) also showed a positive treatment effect (BF = 7.31). Sequential Bayesian analyses provided evidence for reducing IMs of work-related trauma for healthcare workers. This methodology also allowed us to rule out negative effects early, reduced the planned maximum sample size, and allowed evaluation of enhancements. Trial Registration NCT04992390 ( www.clinicaltrials.gov ).

Tidewater-glacier response to supraglacial lake drainage.

The flow speed of the Greenland Ice Sheet changes dramatically in inland regions when surface meltwater drains to the bed. But ice-sheet discharge to the ocean is dominated by fast-flowing outlet glaciers, where the effect of increasing surface melt on annual discharge is unknown. Observations of a supraglacial lake drainage at Helheim Glacier, and a consequent velocity pulse propagating down-glacier, provide a natural experiment for assessing the impact of changes in injected meltwater, and allow us to interrogate the subglacial hydrological system. We find a highly efficient subglacial drainage system, such that summertime lake drainage has little net effect on ice discharge. Our results question the validity of common remote-sensing approaches for inferring subglacial conditions, knowledge of which is needed for improved projections of sea-level rise.

The Impact of Basal Roughness on Inland Thwaites Glacier Sliding.

Swath radar technology enables three-dimensional mapping of modern glacier beds over large areas at resolutions that are higher than those typically used in ice-flow models. These data may enable new understanding of processes at the ice-bed interface. Here, we use two densely surveyed swath-mapped topographies (<50 m2 resolution) of Thwaites Glacier to investigate the sensitivity of inferred basal friction proxies to bed roughness magnitude and orientation. Our work suggests that along-flow roughness influences inferred friction more than transverse-flow roughness, which agrees with analytic form-drag sliding theory. Using our model results, we calculate the slip length (the ratio of internal shear to basal slip). We find excellent agreement between the numerically derived slip lengths and slip lengths predicted by analytic form-drag sliding theory, which suggests that unresolved short wavelength bed roughness may control sliding in the Thwaites interior.

Feasibility, acceptability and costs of nurse-led Alpha-Stim cranial electrostimulation to treat anxiety and depression in university students.

BACKGROUND: Only a relatively low proportion of university students seek help for anxiety and depression disorders, partly because they dislike current drug and psychological treatment options and would prefer home-based care. The aim of this study is to determine the feasibility, acceptability and cost utility of Alpha-Stim cranial electrostimulation (CES) delivered through a nurse led primary care clinic as a daily treatment for anxiety and depression symptoms by the student at home in contrast to usual primary care. METHOD: Feasibility and acceptability of a nurse led clinic offering Alpha-Stim CES in terms of the take up and completion of the six-week course of Alpha-Stim CES. Change in score on the GAD-7 and PHQ-9 as measures of anxiety and depression symptoms at baseline and at 8 weeks following a course of Alpha-Stim CES. Similar evaluation in a non-randomised control group attending a family doctor over the same period. Cost-utility analysis of the nurse led Alpha-Stim CES and family doctor pathways with participants failing to improve following further NICE Guideline clinical care (facilitated self-help and cognitive behaviour therapy). RESULTS: Of 47 students (mean age 22.1, years, 79% female opting for Alpha-Stim CES at the nurse-led clinic 46 (97.9%) completed a 6-week daily course. Forty-seven (47) students comprised a comparison group receiving usual family doctor care. Both Alpha-Stim CES and usual family doctor care were associated with large effect size reductions in GAD-7 and PHQ-9 scores from baseline to 8 weeks. There were no adverse effects and only one participant showed a clinically important deterioration in the Alpha-Stim group. In the cost utility analysis, Alpha-Stim CES was a cheaper option than usual family doctor care under all deterministic or probabilistic assumptions. CONCLUSION: Nurse delivered Alpha-Stim CES may be a feasible, acceptable and cheaper way of providing greater choice and home-based care for some university students seeking help from primary care with new presentations of anxiety and depression.

Validation of the P1vital® Faces Set for Use as Stimuli in Tests of Facial Emotion Recognition.

BACKGROUND: Negative bias in facial emotion recognition is a well-established concept in mental disorders such as depression. However, existing face sets of emotion recognition tests may be of limited use in international research, which could benefit from more contemporary and diverse alternatives. Here, we developed and provide initial validation for the P1vital® Affective Faces set (PAFs) as a contemporary alternative to the widely-used Pictures of Facial Affect (PoFA). METHODS: The PAFs was constructed of 133 color photographs of facial expressions of ethnically-diverse trained actors and compared with the PoFA, comprised of 110 black and white photographs of facial expressions of generally Caucasian actors. Sixty-one recruits were asked to classify faces from both sets over six emotions (happy, sad, fear, anger, disgust, surprise) varying in intensity in 10% increments from 0 to 100%. RESULTS: Participants were significantly more accurate in identifying correct emotions viewing faces from the PAFs. In both sets, participants identified happy faces more accurately than fearful faces, were least likely to misclassify facial expressions as happy and most likely to misclassify all emotions at low intensity as neutral. Accuracy in identifying facial expressions improved with increasing emotion intensity for both sets, reaching peaks at 60 and 80% intensity for the PAFs and PoFA, respectively. The study was limited by small sizes and age-range of participants and ethnic diversity of actors. CONCLUSIONS: The PAFs successfully depicted a range of emotional expressions with improved performance over the PoFA and may be used as a contemporary set in facial expression recognition tests.

Rapid Formation of an Ice Doline on Amery Ice Shelf, East Antarctica.

Surface meltwater accumulating on Antarctic ice shelves can drive fractures through to the ocean and potentially cause their collapse, leading to increased ice discharge from the continent. Implications of increasing surface melt for future ice shelf stability are inadequately understood. The southern Amery Ice Shelf has an extensive surface hydrological system, and we present data from satellite imagery and ICESat-2 showing a rapid surface disruption there in winter 2019, covering ∼60 km2. We interpret this as an ice-covered lake draining through the ice shelf, forming an ice doline with a central depression reaching 80 m depth amidst over 36 m uplift. Flexural rebound modeling suggests 0.75 km3 of water was lost. We observed transient refilling of the doline the following summer with rapid incision of a narrow meltwater channel (20 m wide and 6 m deep). This study demonstrates how high-resolution geodetic measurements can explore critical fine-scale ice shelf processes.

The clinical effectiveness of using a predictive algorithm to guide antidepressant treatment in primary care (PReDicT): an open-label, randomised controlled trial.

Depressed patients often do not respond to the first antidepressant prescribed, resulting in sequential trials of different medications. Personalised medicine offers a means of reducing this delay; however, the clinical effectiveness of personalised approaches to antidepressant treatment has not previously been tested. We assessed the clinical effectiveness of using a predictive algorithm, based on behavioural tests of affective cognition and subjective symptoms, to guide antidepressant treatment. We conducted a multicentre, open-label, randomised controlled trial in 913 medication-free depressed patients. Patients were randomly assigned to have their antidepressant treatment guided by a predictive algorithm or treatment as usual (TaU). The primary outcome was the response of depression symptoms, defined as a 50% or greater reduction in baseline score of the QIDS-SR-16 scale, at week 8. Additional prespecified outcomes included symptoms of anxiety at week 8, and symptoms of depression and functional outcome at weeks 8, 24 and 48. The response rate of depressive symptoms at week 8 in the PReDicT (55.9%) and TaU (51.8%) arms did not differ significantly (odds ratio: 1.18 (95% CI: 0.89-1.56), P = 0.25). However, there was a significantly greater reduction of anxiety in week 8 and a greater improvement in functional outcome at week 24 in the PReDicT arm. Use of the PReDicT test did not increase the rate of response to antidepressant treatment estimated by depressive symptoms but did improve symptoms of anxiety at week 8 and functional outcome at week 24. Our findings indicate that personalisation of antidepressant treatment may improve outcomes in depressed patients.

Vulnerability of Antarctica's ice shelves to meltwater-driven fracture.

Atmospheric warming threatens to accelerate the retreat of the Antarctic Ice Sheet by increasing surface melting and facilitating 'hydrofracturing'1-7, where meltwater flows into and enlarges fractures, potentially triggering ice-shelf collapse3-5,8-10. The collapse of ice shelves that buttress11-13 the ice sheet accelerates ice flow and sea-level rise14-16. However, we do not know if and how much of the buttressing regions of Antarctica's ice shelves are vulnerable to hydrofracture if inundated with water. Here we provide two lines of evidence suggesting that many buttressing regions are vulnerable. First, we trained a deep convolutional neural network (DCNN) to map the surface expressions of fractures in satellite imagery across all Antarctic ice shelves. Second, we developed a stability diagram of fractures based on linear elastic fracture mechanics to predict where basal and dry surface fractures form under current stress conditions. We find close agreement between the theoretical prediction and the DCNN-mapped fractures, despite limitations associated with detecting fractures in satellite imagery. Finally, we used linear elastic fracture mechanics theory to predict where surface fractures would become unstable if filled with water. Many regions regularly inundated with meltwater today are resilient to hydrofracture-stresses are low enough that all water-filled fractures are stable. Conversely, 60 ± 10 per cent of ice shelves (by area) both buttress upstream ice and are vulnerable to hydrofracture if inundated with water. The DCNN map confirms the presence of fractures in these buttressing regions. Increased surface melting17 could trigger hydrofracturing if it leads to water inundating the widespread vulnerable regions we identify. These regions are where atmospheric warming may have the largest impact on ice-sheet mass balance.

Value of monitoring negative emotional bias in primary care in England for personalised antidepressant treatment: a modelling study.

BACKGROUND: Depressed patients often focus on negative life events. Effective antidepressant therapy reverses this negative emotional bias (NEB) within 1 week. Clinical therapeutic effect usually requires 4-6 weeks. The value of implementing NEB monitoring for the personalisation of antidepressant therapy is unknown. OBJECTIVE: To estimate the likely outcome and cost consequences of adopting the P1vital Oxford Emotional Test Battery (ETB) for this purpose in routine primary care in England. METHODS: A hybrid decision analytic model (decision tree plus Markov model) was developed to estimate the cost-effectiveness of ETB monitoring versus no ETB over 52 weeks using quality-adjusted life years (QALYs). Differences in depression severity, episode type and analytical perspectives were considered. Input data were derived from relevant guidelines, literature, national databases, expert opinion and the developers for the year 2013. Multiple sensitivity analyses addressed uncertainty. FINDINGS: The mean number of ETB tests is 2.162 per newly diagnosed patient and 2.166 per patient with recurrent depression. The incremental cost-effectiveness of ETB versus 'no ETB' is £4355/QALY from the healthcare perspective. From the broader societal perspective, ETB is more effective and cost saving. CONCLUSIONS: Monitoring negative emotional bias in primary care in England for personalised antidepressant treatment using ETB seems as an effective and cost-effective option under all considered scenarios (including worst case). Its main economic value seems to lie in reduced productivity loss as opposed to healthcare savings. CLINICAL IMPLICATIONS: The test supports accelerated application of evidence-based depression care. Further optimisation and implementation in the ongoing European PReDicT trial is ongoing.

Predicting treatment response to antidepressant medication using early changes in emotional processing.

Antidepressants must be taken for weeks before response can be assessed with many patients not responding to the first medication prescribed. This often results in long delays before effective treatment is started. Antidepressants induce changes in the processing of emotional stimuli early in the course of treatment. In the current study we assessed whether changes in emotional processing and subjective symptoms over the first week of antidepressant treatment predicted clinical response after 4-8 weeks of treatment. Such a predictive test may shorten the time taken to initiate effective treatment in depressed patients. Seventy-four depressed primary care patients completed measures of emotional bias and subjective symptoms before starting antidepressant treatment and then again 1 week later. Response to treatment was assessed after 4-6 weeks. The performance of classifiers based on these measures was assessed using a leave-one-out validation procedure with the best classifier then tested in an independent sample from a second study of 239 patients. The combination of a facial emotion recognition task and subjective symptoms predicted response with 77% accuracy in the training sample and 60% accuracy in the independent study, significantly better than possible using baseline response rates. The face based measure of emotional bias provided good quality data with high acceptability ratings. Changes in emotional processing can provide a sensitive early measure of antidepressant efficacy for individual patients. Early treatment induced changes in emotional processing may be used to guide antidepressant therapy and reduce the time taken for depressed patients to return to good mental health.

The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial.

BACKGROUND: Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4-6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. METHODS/DESIGN: The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient's antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms - Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. DISCUSSION: This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02790970 . Registered on 30 March 2016.

Corrigendum: Widespread movement of meltwater onto and across Antarctic ice shelves.

This corrects the article DOI: 10.1038/nature22049.

Widespread movement of meltwater onto and across Antarctic ice shelves.

Surface meltwater drains across ice sheets, forming melt ponds that can trigger ice-shelf collapse, acceleration of grounded ice flow and increased sea-level rise. Numerical models of the Antarctic Ice Sheet that incorporate meltwater's impact on ice shelves, but ignore the movement of water across the ice surface, predict a metre of global sea-level rise this century in response to atmospheric warming. To understand the impact of water moving across the ice surface a broad quantification of surface meltwater and its drainage is needed. Yet, despite extensive research in Greenland and observations of individual drainage systems in Antarctica, we have little understanding of Antarctic-wide surface hydrology or how it will evolve. Here we show widespread drainage of meltwater across the surface of the ice sheet through surface streams and ponds (hereafter 'surface drainage') as far south as 85° S and as high as 1,300 metres above sea level. Our findings are based on satellite imagery from 1973 onwards and aerial photography from 1947 onwards. Surface drainage has persisted for decades, transporting water up to 120 kilometres from grounded ice onto and across ice shelves, feeding vast melt ponds up to 80 kilometres long. Large-scale surface drainage could deliver water to areas of ice shelves vulnerable to collapse, as melt rates increase this century. While Antarctic surface melt ponds are relatively well documented on some ice shelves, we have discovered that ponds often form part of widespread, large-scale surface drainage systems. In a warming climate, enhanced surface drainage could accelerate future ice-mass loss from Antarctic, potentially via positive feedbacks between the extent of exposed rock, melting and thinning of the ice sheet.

Antarctic ice shelf potentially stabilized by export of meltwater in surface river.

Meltwater stored in ponds and crevasses can weaken and fracture ice shelves, triggering their rapid disintegration. This ice-shelf collapse results in an increased flux of ice from adjacent glaciers and ice streams, thereby raising sea level globally. However, surface rivers forming on ice shelves could potentially export stored meltwater and prevent its destructive effects. Here we present evidence for persistent active drainage networks-interconnected streams, ponds and rivers-on the Nansen Ice Shelf in Antarctica that export a large fraction of the ice shelf's meltwater into the ocean. We find that active drainage has exported water off the ice surface through waterfalls and dolines for more than a century. The surface river terminates in a 130-metre-wide waterfall that can export the entire annual surface melt over the course of seven days. During warmer melt seasons, these drainage networks adapt to changing environmental conditions by remaining active for longer and exporting more water. Similar networks are present on the ice shelf in front of Petermann Glacier, Greenland, but other systems, such as on the Larsen C and Amery Ice Shelves, retain surface water at present. The underlying reasons for export versus retention remain unclear. Nonetheless our results suggest that, in a future warming climate, surface rivers could export melt off the large ice shelves surrounding Antarctica-contrary to present Antarctic ice-sheet models, which assume that meltwater is stored on the ice surface where it triggers ice-shelf disintegration.