Predicting prognosis for adults with depression using individual symptom data: a comparison of modelling approaches.

BACKGROUND: This study aimed to develop, validate and compare the performance of models predicting post-treatment outcomes for depressed adults based on pre-treatment data. METHODS: Individual patient data from all six eligible randomised controlled trials were used to develop (k = 3, n = 1722) and test (k = 3, n = 918) nine models. Predictors included depressive and anxiety symptoms, social support, life events and alcohol use. Weighted sum scores were developed using coefficient weights derived from network centrality statistics (models 1-3) and factor loadings from a confirmatory factor analysis (model 4). Unweighted sum score models were tested using elastic net regularised (ENR) and ordinary least squares (OLS) regression (models 5 and 6). Individual items were then included in ENR and OLS (models 7 and 8). All models were compared to one another and to a null model (mean post-baseline Beck Depression Inventory Second Edition (BDI-II) score in the training data: model 9). Primary outcome: BDI-II scores at 3-4 months. RESULTS: Models 1-7 all outperformed the null model and model 8. Model performance was very similar across models 1-6, meaning that differential weights applied to the baseline sum scores had little impact. CONCLUSIONS: Any of the modelling techniques (models 1-7) could be used to inform prognostic predictions for depressed adults with differences in the proportions of patients reaching remission based on the predicted severity of depressive symptoms post-treatment. However, the majority of variance in prognosis remained unexplained. It may be necessary to include a broader range of biopsychosocial variables to better adjudicate between competing models, and to derive models with greater clinical utility for treatment-seeking adults with depression.

Role of age, gender and marital status in prognosis for adults with depression: An individual patient data meta-analysis.

AIMS: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8, and 9-12 months post-baseline and remission at 3-4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/. RESULTS: There was no evidence of an association between age and prognosis before or after adjusting for depressive 'disorder characteristics' that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3-4 months post-baseline per-5-year increase in age = 0(95% CI: -0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3-4 months or 9-12 months post-baseline, but men had worse prognoses at 6-8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6-8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive 'disorder characteristics' and employment status (12.23% (-1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive 'disorder characteristics' and all available confounders. CONCLUSION: Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive 'disorder characteristics' in clinic may be important.

The importance of transdiagnostic symptom level assessment to understanding prognosis for depressed adults: analysis of data from six randomised control trials.

BACKGROUND: Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety comorbidity, and consider the association of a wide range of symptoms with treatment outcomes. METHOD: Individual patient data from six RCTs of depressed patients (total n = 2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention time points using individual items and sum scores. Symptom networks (graphical Gaussian model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators. RESULTS: Item-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms. CONCLUSION: The relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology.

The Mars 2020 Engineering Cameras and Microphone on the Perseverance Rover: A Next-Generation Imaging System for Mars Exploration.

The Mars 2020 Perseverance rover is equipped with a next-generation engineering camera imaging system that represents an upgrade over previous Mars rover missions. These upgrades will improve the operational capabilities of the rover with an emphasis on drive planning, robotic arm operation, instrument operations, sample caching activities, and documentation of key events during entry, descent, and landing (EDL). There are a total of 16 cameras in the Perseverance engineering imaging system, including 9 cameras for surface operations and 7 cameras for EDL documentation. There are 3 types of cameras designed for surface operations: Navigation cameras (Navcams, quantity 2), Hazard Avoidance Cameras (Hazcams, quantity 6), and Cachecam (quantity 1). The Navcams will acquire color stereo images of the surface with a 96 ∘ × 73 ∘ field of view at 0.33 mrad/pixel. The Hazcams will acquire color stereo images of the surface with a 136 ∘ × 102 ∘ at 0.46 mrad/pixel. The Cachecam, a new camera type, will acquire images of Martian material inside the sample tubes during caching operations at a spatial scale of 12.5 microns/pixel. There are 5 types of EDL documentation cameras: The Parachute Uplook Cameras (PUCs, quantity 3), the Descent stage Downlook Camera (DDC, quantity 1), the Rover Uplook Camera (RUC, quantity 1), the Rover Descent Camera (RDC, quantity 1), and the Lander Vision System (LVS) Camera (LCAM, quantity 1). The PUCs are mounted on the parachute support structure and will acquire video of the parachute deployment event as part of a system to characterize parachute performance. The DDC is attached to the descent stage and pointed downward, it will characterize vehicle dynamics by capturing video of the rover as it descends from the skycrane. The rover-mounted RUC, attached to the rover and looking upward, will capture similar video of the skycrane from the vantage point of the rover and will also acquire video of the descent stage flyaway event. The RDC, attached to the rover and looking downward, will document plume dynamics by imaging the Martian surface before, during, and after rover touchdown. The LCAM, mounted to the bottom of the rover chassis and pointed downward, will acquire 90 ∘ × 90 ∘ FOV images during the parachute descent phase of EDL as input to an onboard map localization by the Lander Vision System (LVS). The rover also carries a microphone, mounted externally on the rover chassis, to capture acoustic signatures during and after EDL. The Perseverance rover launched from Earth on July 30th, 2020, and touchdown on Mars is scheduled for February 18th, 2021.

Prioritising physical and psychological symptoms: what are the barriers and facilitators to the discussion of anxiety in the primary care consultation?

BACKGROUND: Anxiety is under-recorded and under-treated in the UK and is under-represented in research compared with depression. Detecting anxiety can be difficult because of co-existing conditions. GPs can be reluctant to medicalise anxiety symptoms and patients can be reluctant to disclose them, for a variety of reasons. This research addresses the gap in evidence of real-life consultations of patients with anxiety and explores how physical and psychological symptoms are discussed and prioritised by patients and GPs in primary care consultations. METHODS: A mixed methods study using a baseline questionnaire, video-recorded primary care consultations and interview data with patients and GPs. RESULTS: Seventeen patients with anxiety symptoms (GAD-7 score ≥ 10) completed a questionnaire, had their consultation video-recorded and took part in a semi-structured interview. Four GPs were interviewed. The main themes that emerged from GP and patients accounts as barriers and facilitators to discussing anxiety mostly mirrored each other. The GP/patient relationship and continuity of care was the main facilitator for the discussion of anxiety in the consultation. The main barriers were: attribution of or unacknowledged symptoms; co-morbidities; and time constraints. GPs overcame these barriers by making repeat appointments and employing prioritising techniques; patients by choosing an empathetic GP. CONCLUSIONS: The findings add to the evidence base concerning the management of anxiety in primary care. The findings suggest that the discussion around anxiety is a process negotiated between the patient and the GP influenced by a range of barriers and facilitators. Co-existing depression and health anxieties can mask anxiety symptoms in patients. Good practice techniques such as bringing back patients for appointments to foster continuity of care and understanding can help disclosure and detection of anxiety symptoms. Future research could investigate this longitudinally and should include a wider range of GPs practices and GPs.

Quantum walks: The first detected passage time problem.

Even after decades of research, the problem of first passage time statistics for quantum dynamics remains a challenging topic of fundamental and practical importance. Using a projective measurement approach, with a sampling time τ, we obtain the statistics of first detection events for quantum dynamics on a lattice, with the detector located at the origin. A quantum renewal equation for a first detection wave function, in terms of which the first detection probability can be calculated, is derived. This formula gives the relation between first detection statistics and the solution of the corresponding Schrödinger equation in the absence of measurement. We illustrate our results with tight-binding quantum walk models. We examine a closed system, i.e., a ring, and reveal the intricate influence of the sampling time τ on the statistics of detection, discussing the quantum Zeno effect, half dark states, revivals, and optimal detection. The initial condition modifies the statistics of a quantum walk on a finite ring in surprising ways. In some cases, the average detection time is independent of the sampling time while in others the average exhibits multiple divergences as the sampling time is modified. For an unbounded one-dimensional quantum walk, the probability of first detection decays like (time)^{(-3)} with superimposed oscillations, with exceptional behavior when the sampling period τ times the tunneling rate γ is a multiple of π/2. The amplitude of the power-law decay is suppressed as τ→0 due to the Zeno effect. Our work, an extended version of our previously published paper, predicts rich physical behaviors compared with classical Brownian motion, for which the first passage probability density decays monotonically like (time)^{-3/2}, as elucidated by Schrödinger in 1915.

Intradiurnal Fluctuations of Off-Resonance Saturation Effects in Healthy Human Achilles Tendons Assessed with a 3D Ultrashort Echo Time MRI Sequence at 3 Tesla.

PURPOSE: The purpose of this study was to evaluate whether gravitational interstitial fluid accumulation in healthy subjects has an impact on off-resonance saturation ratios (OSR) or the volume of the Achilles tendon after a prolonged time of reduced levels of physical activity. MATERIALS AND METHODS: 7 healthy volunteers were repeatedly investigated on 3 consecutive days on a 3 T whole body MR scanner using an ultrashort echo time (UTE) imaging sequence with a Gaussian off-resonance saturation pulse at a frequency offset of 2000 Hz to calculate OSR values. For accurate volumetric quantification of the Achilles tendon, a newly developed contour detection snake algorithm was applied on high-resolution isotropic T2-weighted SPACE sequence datasets. Single-measure intraclass correlation coefficients (ICC) were calculated to estimate test-retest reliability. RESULTS: For OSR and tendon volume measurements on three consecutive days, excellent reproducibility could be achieved with ICC values above 0.96 and 0.97, respectively. Comparing the results of all three days, a statistically significant mean individual percentage decrease (- 4.1  ±â€Š1.5 %; p = 0.001) of calculated tendon OSR values was found for the evening measurements. No statistically significant difference between tendon volumes in the morning and the evening could be detected (p = 0.589). CONCLUSION: The results of this in-vivo study demonstrate a significant influence of gravitational interstitial fluid accumulation after reduced physical activity on OSR values in the Achilles tendon, but not on tendon volume. Taken together with the demonstrated excellent reproducibility, these findings are important for future studies investigating temporal changes of the Achilles tendon microstructure.

Use of snacks in insulin-treated people with diabetes mellitus and association with HbA1c , weight and quality of life: a cross sectional study.

AIM: Insulin therapies with prandial injections offer the possibility to skip snacks or omit meals. It is unclear how many people with insulin-treated diabetes mellitus eat snacks and whether they snack for their own comfort or only on the recommendation of healthcare professionals. METHODS: In 2004, 163 consecutive people with insulin-treated diabetes seen in a university outpatient department were interviewed regarding their diet and degree of satisfaction with their meals. Fifty-five had Type 1 diabetes [age 47 years; diabetes duration 18 years; BMI 27 kg/m(2) ; HbA1c 62 mmol/mol (7.8%)], 53 had Type 2 diabetes with biphasic insulin therapy [age 68 years; diabetes duration 17 years; BMI 31 kg/m(2) ; HbA1c 60 mmol/mol (7.6%)] and 55 had Type 2 diabetes with prandial insulin therapy [age 60 years; diabetes duration 16 years; BMI 33 kg/m(2) ; HbA1c 59 mmol/mol (7.6%)]. RESULTS: Eighty per cent of those with Type 1 diabetes ate snacks, together with 77% of the Type 2 diabetes/biphasic group and 62% of the Type 2 diabetes/prandial group. Most participants (91% Type 1 diabetes, 88% Type 2 diabetes/biphasic group, 82% Type 2 diabetes/prandial group) liked to have snacks. The time at which they ate snacks was the same for both diabetes types. There were no differences between participants with Type 1 diabetes who snacked and those who did not in terms of age (P = 0.350), BMI (P = 0.368), HbA1c (P = 0.257) and time since diagnosis (P = 0.846). Participants with Type 2 diabetes who ate snacks were older than those who did not (biphasic: P = 0.006; prandial: P = 0.008). There were no differences in terms of BMI (biphasic: P = 0.731; prandial: P = 0.393), HbA1c (biphasic: P = 0.747; prandial: P = 0.616) and time since diagnosis (biphasic: P = 0.06; prandial: P = 0.620). CONCLUSIONS: Most people with insulin-treated diabetes eat snacks voluntarily and not because of physicians' instructions. There were no correlations between the use of snacks and HbA1c , BMI and time since diagnosis, except that the participants with Type 2 diabetes who ate snacks were older.

Superaging correlation function and ergodicity breaking for Brownian motion in logarithmic potentials.

We consider an overdamped Brownian particle moving in a confining asymptotically logarithmic potential, which supports a normalized Boltzmann equilibrium density. We derive analytical expressions for the two-time correlation function and the fluctuations of the time-averaged position of the particle for large but finite times. We characterize the occurrence of aging and nonergodic behavior as a function of the depth of the potential, and we support our predictions with extensive Langevin simulations. While the Boltzmann measure is used to obtain stationary correlation functions, we show how the non-normalizable infinite covariant density is related to the superaging behavior.

Gas-phase detonation propagation in mixture composition gradients.

The propagation of detonations through several fuel-air mixtures with spatially varying fuel concentrations is examined numerically. The detonations propagate through two-dimensional channels, inside of which the gradient of mixture composition is oriented normal to the direction of propagation. The simulations are performed using a two-component, single-step reaction model calibrated so that one-dimensional detonation properties of model low- and high-activation-energy mixtures are similar to those observed in a typical hydrocarbon-air mixture. In the low-activation-energy mixture, the reaction zone structure is complex, consisting of curved fuel-lean and fuel-rich detonations near the line of stoichiometry that transition to decoupled shocks and turbulent deflagrations near the channel walls where the mixture is extremely fuel-lean or fuel-rich. Reactants that are not consumed by the leading detonation combine downstream and burn in a diffusion flame. Detonation cells produced by the unstable reaction front vary in size across the channel, growing larger away from the line of stoichiometry. As the size of the channel decreases relative to the size of a detonation cell, the effect of the mixture composition gradient is lessened and cells of similar sizes form. In the high-activation-energy mixture, detonations propagate more slowly as the magnitude of the mixture composition gradient is increased and can be quenched in a large enough gradient.

Investigation of thyroid dysfunction is more likely in patients with high psychological morbidity.

BACKGROUND: Mild or subclinical hypothyroidism [raised thyroid-stimulating hormone (TSH) but normal free thyroxine (T4)] affects 5-10% of adults. Symptoms are non-specific and TSH levels are needed for diagnosis. OBJECTIVES: We explore the relationship between thyroid function and psychological distress and investigate the usefulness of an expert-designed Thyroid Symptom Questionnaire (TSQ) in identifying hypothyroidism. METHODS: DEPTH (DEPression and THyroid) is a cross-sectional study of 325 patients recruited from general practices in Bristol, for whom thyroid function tests were requested by the GP. Subjects completed the TSQ, General Health Questionnaire (GHQ-12) and Patient Health Questionnaire (PHQ) and had blood tests for TSH and free T4. RESULTS: The mean age was 45.7 years; 252 subjects (78%) were female; median TSH was 1.6. Psychological morbidity in this population is high: 54.2% have a GHQ-12 score >3, indicating psychological distress. We found no relationship between TSH and psychological distress [adjusted odds ratio 1.02 (95% confidence interval 0.91-1.13), P = 0.78]. The prevalence of hypothyroidism was 6.2% (95% confidence interval 3.8-9.5%). We found no evidence of an unadjusted association between TSQ score and subclinical hypothyroidism [adjusted odds ratio of 1.09 (95% confidence interval 0.95-1.24), P = 0.23]. CONCLUSIONS: Those referred for thyroid function tests, although no more likely than others to have hypothyroidism, have high rates of psychological distress. When mild (subclinical) hypothyroidism is detected in patients with psychological distress, it is important that GPs are aware that this is likely to be coincidental rather than causal and offer appropriate treatment.

[Vocational interventions integrated in inpatient rehabilitation]. / Medizinisch-berufliche Interventionen in der stationären orthopädischen Rehabilitation. Explorative Evaluation eines Pilot-projektes aus Patientensicht.

Orientation on work place associated problems is a typical assignment of medical rehabilitation in Germany. The implementation of special vocational programmes, however, may be associated with several challenges concerning staff and space required, which could be difficult to overcome.

Fluctuations of time averages for Langevin dynamics in a binding force field.

We derive a simple formula for the fluctuations of the time average x(t) around the thermal mean (eq) for overdamped brownian motion in a binding potential U(x). Using a backward Fokker-Planck equation, introduced by Szabo, Schulten, and Schulten in the context of reaction kinetics, we show that for ergodic processes these finite measurement time fluctuations are determined by the Boltzmann measure. For the widely applicable logarithmic potential, ergodicity is broken. We quantify the large nonergodic fluctuations and show how they are related to a superaging correlation function.

No clear evidence of an association between plasma concentrations of n-3 long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population.

Previous research suggests that low n-3 long-chain polyunsaturated fatty acid (n-3PUFA) status is associated with higher levels of depression in clinical populations. This analysis aimed to investigate the relationship between depressed mood and n-3PUFA status in a non-clinical population. The analysis was conducted on data collected as part of a large randomized controlled trial investigating the impact of n-3PUFA supplementation on depressed mood in a community-based population. On entry into the trial, data on depressed mood were collected using the Depression, Anxiety and Stress Scales (DASS) and the Beck Depression Inventory (BDI). Plasma concentrations of various n-3PUFAs and n-6 long-chain polyunsaturated fatty acids (n-6PUFAs) were obtained from fasting venous blood samples, and various demographics were also measured. Using regression, there was no evidence of an association between either measure of depressed mood and any of the measures of n-3PUFA status or of n-6PUFA:n-3PUFA ratios. Clear associations were also not found when demographic factors were included in the analyses. These findings suggest that n-3PUFAs may not have a role in the aetiology of minor depression. This is also consistent with the results of other studies that have not demonstrated an association between depressed mood and n-3PUFA status in non-clinical populations and epidemiological studies that have not demonstrated an association between depressed mood and n-3PUFA intake in these populations.

Assessing mental health in primary care research using standardized scales: can it be carried out over the telephone?

BACKGROUND: Telephone interviewing has economic and logistical advantages but has not been widely used in the UK. Most studies comparing face-to-face and telephone psychiatric assessment have been carried out in the US, often restricted to a population with known psychiatric disorder and involving comparisons between two separate sample groups rather than repeat interviews with the same group. The aim of the present study was to compare face-to-face and telephone administration of the 12-item General Health Questionnaire and the Revised Clinical Interview Schedule in a UK general practice sample. METHOD: Ninety-eight consecutive attenders at two general practices were assessed twice within 48 h. The order of face-to-face and telephone interviews was alternated. RESULTS: There was no evidence that the mode of administration led to a bias in scores on the CIS-R. For the GHQ, those aged over 60 tended to score higher on the telephone. There was good agreement between face-to-face and telephone scores for both GHQ and CIS-R and good agreement for case definition. Participants had a strong preference for face-to-face interviews. CONCLUSIONS: Telephone assessment of mental health using the GHQ and CIS-R is a reasonable method to be used in primary care research in the UK with the limitation that telephone responses from older people might be different from face-to-face assessments for the GHQ. However, telephone interviewing appeared less acceptable and should probably be used in the context of established or ongoing personal contact between researcher and subject.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia (ARVD/C) is one cause of death in young adults in the United States, representing approximately 17% of all ARVD/C cases reported. This study presents 2 cases of ARVD/C diagnosed at a central Texas hospital and reviews the literature regarding this disease. The diagnosis, histology, presentation, prognosis, and therapy are addressed because the rare nature of this disease within the United States makes diagnosis and treatment difficult and creates problems of adaptation for the patient. Clinicians must become more familiar with this potentially fatal cardiac disorder that can create vulnerability within a young adult population.