Neuropsychological and functional outcomes in recent-onset major depression, bipolar disorder and schizophrenia-spectrum disorders: a longitudinal cohort study

Functional disability is the lead contributor to burden of mental illness. Cognitive deficits frequently limit functional recovery, although whether changes in cognition and disability are longitudinally associated in recent-onset individuals remains unclear. Using a prospective, cohort design, 311 patients were recruited and assessed at baseline. One hundred and sixty-seven patients met eligibility criteria (M = 21.5 years old, s.d. = 4.8) and returned for follow-up (M = 20.6 months later, s.d. = 7.8). Two-hundred and thirty participants were included in the final analysis, comprising clinically stable patients with major depression (n = 71), bipolar disorder (BD; n = 61), schizophrenia-spectrum disorders (n = 35) and 63 healthy controls. Neuropsychological functioning and self-rated functional disability were examined using mixed-design, repeated-measures analysis, across diagnoses and cognitive clusters, covarying for relevant confounds. Clinical, neuropsychological and functional changes did not differ between diagnoses (all P40.05). Three reliable neuropsychological subgroups emerged through cluster analysis, characterized by psychomotor slowing, improved sustained attention, and improved verbal memory. Controlling for diagnosis and changes in residual symptoms, clusters with improved neuropsychological functioning observed greater reductions in functional disability than the psychomotor slowing cluster, which instead demonstrated a worsening in disability (Po0.01). Improved sustained attention was independently associated with greater likelihood of follow-up employment (Po0.01). Diagnosis of BD uniquely predicted both follow-up employment and independent living. Neuropsychological course appears to be independently predictive of subjective and objective functional outcomes. Importantly, cognitive phenotypes may reflect distinct pathophysiologies shared across major psychiatric conditions, and be ideal targets for personalized early intervention

Transitions:comparing timescales of eruption and evacuation at Volcán de Fuego (Guatemala) to understand relationships between hazard evolution and responsive action

During volcanic crisis, effective risk mitigation requires that institutions and local people respond promptly to protect lives and livelihoods. In this paper, we ask: over what timescales do explosive paroxysmal eruptions evolve? And how do these timescales relate to those of people’s past responses? We explore these questions by comparing timescales of eruptions and evacuations for several recent events at Volcán de Fuego (Guatemala) to identify lags in evacuation and determine the drivers of these lags. We use multiple geophysical datasets for explosive paroxysmal eruptions (“paroxysms”) in 2012–2018 to constrain timescales of eruptive evolution. In parallel, we determine timescales of response and the impacts of uncertainty and eruptive behaviours on decision-making through interviews with institutional and local actors. We then compare eruption and response timescales to explore the drivers for decision-making, whether volcanic, institutional, or personal. We find that eruption and response timescales are comparable. However, we also find that periods of decision-making and warning dissemination delay response until well after eruptive onset. We document how in recent eruptions, response occurs during eruptive climax when risk is at peak. We use paired timelines to elucidate the key drivers of this ‘response lag’ and show that despite the high levels of forecasting uncertainty, response times could be improved by agreed means to collaborate through shared information and agreed actions. We conclude by considering how the analysis presented here might be useful to different actors who share the goal of preserving lives and livelihoods at Fuego, focussing on how community’s needs can be met such that during an eruptive crisis the community can evacuate in time. Our analysis offers practical insights for people working to mitigate risk to populations near active volcanoes around the world.</p

Eruption frequency patterns through time for the current (1999–2018) activity cycle at Volcán de Fuego derived from remote sensing data:Evidence for an accelerating cycle of explosive paroxysms and potential implications of eruptive activity

Volcán de Fuego is a stratovolcano in Guatemala that has produced over 50 VEI ≥ 2 eruptions since 1524. After two decades of quiescence, in 1999 Fuego entered a new period of eruptive activity that continues until the present day, characterized by persistent Strombolian activity interspersed with occasional “paroxysmal” eruptions of greater magnitude, the most recent of which occurred in 2018. The land surrounding Fuego accommodates tens of thousands of people, so greater understanding of its eruptive behaviour has important implications for hazard assessment. Nevertheless, there is relatively little literature that studies recent (since 1999) activity of Fuego in detail. Using time-series analysis of remote sensing thermal data during the period 2000–2018 combined with recent bulletin reports, we present evidence for a new eruptive regime beginning in 2015. We find that this regime is defined by a greater frequency of paroxysmal eruptions than in previous years and is characterized by the following sequence of events: (i) effusion of lava flows and increase in summit explosive activity, followed by (ii) an intense eruptive phase lasting 24–48 h, producing a sustained eruptive column, continuous explosions, and occasional pyroclastic flows, followed by (iii) decrease in explosive activity. We discuss various models that explain this increase in paroxysmal frequency, and consider its implications for hazard assessment at Fuego. We advocate the pairing of remote sensing data with monitoring reports for understanding long-term changes in behaviour of poorly-instrumented volcanoes. The results that we present here provide a standard for informed assessment of future episodes of unrest and paroxysmal eruptions of Fuego

Derivation of dose/volume constraints for the anorectum from clinician and patient-reported outcomes in the CHHiP trial of radiotherapy fractionation.

BACKGROUND:The CHHiP trial randomised 3216 men with localised prostate cancer (1:1:1) to three radiotherapy fractionation schedules: 74Gy/37 fractions (f) over 7.4 weeks, 60Gy/20f/4 weeks and 57Gy/19f/3.8 weeks. Literature-based dose constraints were applied with arithmetic adjustment for the hypofractionated arms. This study aimed to derive anorectal dose constraints using prospectively-collected clinician-reported outcomes (CRO) and patient-reported outcomes (PRO) and to assess the added predictive value of spatial dose metrics. METHODS:A case-control study design was used, seven CRO and five PRO bowel symptoms were evaluated. Cases experienced a moderate or worse symptom 1-5 years post-radiotherapy, and did not have the symptom pre-radiotherapy. Controls did not experience the symptom at baseline, or between 1-5 years post-radiotherapy. The anorectum was re-contoured from the anal verge to the recto-sigmoid junction; dose/volume parameters were extracted. Univariate logistic regression, atlases of complication indices and bootstrapped receiver-operating-characteristic (ROC) analysis (1000 replicates, balanced outcomes) were used to derive dose constraints for the whole cohort (hypofractionated schedules were converted to 2Gy equivalent schedules using α/β=3Gy) and separate hypofractionated/conventional fractionation cohorts. Only areas under the curve (AUC) with 95% confidence interval lower limits >0.5 were considered statistically significant. Any constraint derived in <95-99% of bootstraps was excluded. RESULTS:Statistically significant dose constraints were derived for CRO, but not PRO. Intermediate to high doses were important for rectal bleeding whereas intermediate doses were important for increased bowel frequency, faecal incontinence and rectal pain. Spatial dose metrics did not improve prediction of CRO or PRO. A new panel of dose constraints for hypofractionated schedules to 60Gy or 57Gy are V20Gy<85%, V30Gy<57%, V40Gy<38%, V50Gy<22% and V60Gy<0.01%. CONCLUSIONS:Dose constraints differed between symptoms, indicating potentially different pathogenesis of radiation-induced side effects. Derived dose constraints were stricter than those used in CHHiP and may reduce bowel symptoms post-radiotherapy

Characterising Australian memory clinics: current practice and service needs informing national service guidelines

Background: Memory clinics (MCs) play a key role in accurate and timely diagnoses and treatment of dementia and mild cognitive impairment. However, within Australia, there are little data available on current practices in MCs, which hinder international comparisons for best practice, harmonisation efforts and national coordination. Here, we aimed to characterise current service profiles of Australian MCs. Methods: The ‘Australian Dementia Network Survey of Expert Opinion on Best Practice and the Current Clinical Landscape’ was conducted between August-September 2020 as part of a larger-scale Delphi process deployed to develop national MC guidelines. In this study, we report on the subset of questions pertaining to current practice including wait-times and post-diagnostic care. Results: Responses were received from 100 health professionals representing 60 separate clinics (45 public, 11 private, and 4 university/research clinics). The majority of participants were from clinics in metropolitan areas (79%) and in general were from high socioeconomic areas. While wait-times varied, only 28.3% of clinics were able to offer an appointment within 1-2 weeks for urgent referrals, with significantly more private clinics (58.3%) compared to public clinics (19.5%) being able to do so. Wait-times were less than 8 weeks for 34.5% of non-urgent referrals. Only 20.0 and 30.9% of clinics provided cognitive interventions or post-diagnostic support respectively, with 7.3% offering home-based reablement programs, and only 12.7% offering access to group-based education. Metropolitan clinics utilised neuropsychological assessments for a broader range of cases and were more likely to offer clinical trials and access to research opportunities. Conclusions: In comparison to similar countries with comprehensive government-funded public healthcare systems (i.e., United Kingdom, Ireland and Canada), wait-times for Australian MCs are long, and post-diagnostic support or evidence-based strategies targeting cognition are not common practice. The timely and important results of this study highlight a need for Australian MCs to adopt a more holistic service of multidisciplinary assessment and post-diagnostic support, as well as the need for the number of Australian MCs to be increased to match the rising number of dementia cases

Analyzing Explosive Volcanic Deposits From Satellite‐Based Radar Backscatter, Volcán de Fuego, 2018

Satellite radar backscatter has the potential to provide useful information about the progression of volcanic eruptions when optical, ground-based, or radar phase-based measurements are limited. However, backscatter changes are complex and challenging to interpret: explosive deposits produce different signals depending on pre-existing ground cover, radar parameters and eruption characteristics. We use high temporal- and spatial-resolution backscatter imagery to examine the emplacement and alteration of pyroclastic density currents (PDCs), lahar and ash deposits from the June 2018 eruption of Volcán de Fuego, Guatemala, using observatory reports and rainfall gauge data to ground truth our observations. We use a temporally dense time series of backscatter data to reduce noise and extract deposit areas. We observe backscatter changes in six drainages, the largest deposit was 11.9-km-long that altered an area of 6.3 urn:x-wiley:21699313:media:jgrb55183:jgrb55183-math-0001 and had a thickness of 10.5 urn:x-wiley:21699313:media:jgrb55183:jgrb55183-math-00022 m in the lower sections as estimated from radar shadows. The 3 June eruption also produced backscatter signal over an area of 40 urn:x-wiley:21699313:media:jgrb55183:jgrb55183-math-0003, consistent with reported ashfall. We use transient patterns in backscatter time series to identify nine periods of high lahar activity in a single drainage system between June and October 2018. We find that the characterisation of subtle backscatter signals associated with explosive eruptions are best observed with (1) radiometric terrain calibration, (2) speckle correction, and (3) consideration of pre-existing scattering properties. Our observations demonstrate that SAR backscatter can capture the emplacement and subsequent alteration of a range of explosive deposits, allowing the progression of an explosive eruption to be monitored

Circadian profiles in young people during the early stages of affective disorder

Although disturbances of the circadian system are strongly linked to affective disorders, no known studies have examined melatonin profiles in young people in early stages of illness. In this study, 44 patients with an affective disorder underwent clinical and neuropsychological assessments. They were then rated by a psychiatrist according to a clinical staging model and were categorized as having an ‘attenuated syndrome' or an ‘established disorder'. During the evening, salivary melatonin was sampled under dim light conditions over an 8-h interval and for each patient, the time of melatonin onset, total area under the curve and phase angle (difference between time of melatonin onset and time of habitual sleep onset) were computed. Results showed that there was no difference in the timing of melatonin onset across illness stages. However, area under the curve analyses showed that those patients with ‘established disorders' had markedly reduced levels of melatonin secretion, and shorter phase angles, relative to those with ‘attenuated syndromes'. These lower levels, in turn, were related to lower subjective sleepiness, and poorer performance on neuropsychological tests of verbal memory. Overall, these results suggest that for patients with established illness, dysfunction of the circadian system relates clearly to functional features and markers of underlying neurobiological change. Although the interpretation of these results would be greatly enhanced by control data, this work has important implications for the early delivery of chronobiological interventions in young people with affective disorders

Internet-based treatment for older adults with depression and co-morbid cardiovascular disease: protocol for a randomised, double-blind, placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Depression, cardiovascular disease (CVD) risk factors and cognitive impairment are important causes of disability and poor health outcomes. In combination they lead to an even worse prognosis. Internet or web-based interventions have been shown to deliver efficacious psychological intervention programs for depression on a large scale, yet no published studies have evaluated their impact among patients with co-existing physical conditions. The aims of this randomised controlled trial are to determine the effects of an evidence-based internet intervention program for depression on depressive mood symptoms, cognitive function and treatment adherence in patients at risk of CVD.</p> <p>Methods/Design</p> <p>This study is an internet-based, double-blind, parallel group randomised controlled trial. The trial will compare the effectiveness of online cognitive behavioural therapy with an online attention control placebo. The trial will consist of a 12-week intervention phase with a 40-week follow-up. It will be conducted in urban and rural New South Wales, Australia and will recruit a community-based sample of adults aged 45 to 75 years. Recruitment, intervention, cognitive testing and follow-up data collection will all be internet-based and automated. The primary outcome is a change in severity of depressive symptoms from baseline to three-months. Secondary outcomes are changes in cognitive function and adherence to treatment for CVD from baseline to three, six and 12-months.</p> <p>Discussion</p> <p>Prior studies of depression amongst patients with CVD have targeted those with previous vascular events and major depression. The potential for intervening earlier in these disease states appears to have significant potential and has yet to be tested. Scalable psychological programs using web-based interventions could deliver care to large numbers in a cost effective way if efficacy were proved. This study will determine the effects of a web-based intervention on depressive symptoms and adherence to treatment among patients at risk of CVD. In addition it will also precisely and reliably define the effects of the intervention upon aspects of cognitive function that are likely to be affected early in at risk individuals, using sensitive and responsive measures.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12610000085077.aspx">ACTRN12610000085077</a></p