Assessing prospective and retrospective metacognitive accuracy following traumatic brain injury remotely across cognitive domains.

The ability to monitor one's behaviour is frequently impaired following TBI, impacting on patients' rehabilitation. Inaccuracies in judgement or self-reflection of one's performance provides a useful marker of metacognition. However, metacognition is rarely measured during routine neuropsychology assessments and how it varies across cognitive domains is unclear. A cohort of participants consisting of 111 TBI patients [mean age = 45.32(14.15), female = 29] and 84 controls [mean age = 31.51(12.27), female = 43] was studied. Participants completed cognitive assessments via a bespoke digital platform on their smartphones. Included in the assessment were a prospective evaluation of memory and attention, and retrospective confidence judgements of task performance. Metacognitive accuracy was calculated from the difference between confidence judgement of task performance and actual performance. Prospective judgment of attention and memory was correlated with task performance in these domains for controls but not patients. TBI patients had lower task performance in processing speed, executive functioning and working memory compared to controls, maintaining high confidence, resulting in overestimation of cognitive performance compared to controls. Additional judgments of task performance complement neuropsychological assessments with little additional time-cost. These results have important theoretical and practical implications for evaluation of metacognitive impairment in TBI patients and neurorehabilitation.

Player position in American football influences the magnitude of mechanical strains produced in the location of chronic traumatic encephalopathy pathology: A computational modelling study.

American football players are frequently exposed to head impacts, which can cause concussions and may lead to neurodegenerative diseases such as chronic traumatic encephalopathy (CTE). Player position appears to influence the risk of concussion but there is limited work on its effect on the risk of CTE. Computational modelling has shown that large brain deformations during head impacts co-localise with CTE pathology in sulci. Here we test whether player position has an effect on brain deformation within the sulci, a possible biomechanical trigger for CTE. We physically reconstructed 148 head impact events from video footage of American Football games. Players were separated into 3 different position profiles based on the magnitude and frequency of impacts. A detailed finite element model of TBI was then used to predict Green-Lagrange strain and strain rate across the brain and in sulci. Using a one-way ANOVA, we found that in positions where players were exposed to large magnitude and low frequency impacts (e.g. defensive back and wide receiver), strain and strain rate across the brain and in sulci were highest. We also found that rotational head motion is a key determinant in producing large strains and strain rates in the sulci. Our results suggest that player position has a significant effect on impact kinematics, influencing the magnitude of deformations within sulci, which spatially corresponds to where CTE pathology is observed. This work can inform future studies investigating different player-position risks for concussion and CTE and guide design of prevention systems.

SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes.

OBJECTIVES: To understand SARS-Co-V-2 infection and transmission in UK nursing homes in order to develop preventive strategies for protecting the frail elderly residents. METHODS: An outbreak investigation involving 394 residents and 70 staff, was carried out in 4 nursing homes affected by COVID-19 outbreaks in central London. Two point-prevalence surveys were performed one week apart where residents underwent SARS-CoV-2 testing and had relevant symptoms documented. Asymptomatic staff from three of the four homes were also offered SARS-CoV-2 testing. RESULTS: Overall, 26% (95% CI 22-31) of residents died over the two-month period. All-cause mortality increased by 203% (95% CI 70-336) compared with previous years. Systematic testing identified 40% (95% CI 35-46) of residents as positive for SARS-CoV-2, and of these 43% (95% CI 34-52) were asymptomatic and 18% (95% CI 11-24) had only atypical symptoms; 4% (95% CI -1 to 9) of asymptomatic staff also tested positive. CONCLUSIONS: The SARS-CoV-2 outbreak in four UK nursing homes was associated with very high infection and mortality rates. Many residents developed either atypical or had no discernible symptoms. A number of asymptomatic staff members also tested positive, suggesting a role for regular screening of both residents and staff in mitigating future outbreaks.

Diffusion tensor imaging reveals changes in microstructural integrity along compressed nerve roots that correlate with chronic pain symptoms and motor deficiencies in elderly stenosis patients.

Age-related degenerative changes in the lumbar spine frequently result in nerve root compression causing severe pain and disability. Given the increasing incidence of lumbar spinal disorders in the aging population and the discrepancies between the use of current diagnostic imaging tools and clinical symptoms, novel methods of nerve root assessment are needed. We investigated elderly patients with stenosis at L4-L5 or L5-S1 levels. Diffusion tensor imaging (DTI) was used to quantify microstructure in compressed L5 nerve roots and investigate relationships to clinical symptoms and motor neurophysiology. DTI metrics (i.e. FA, MD, AD and RD) were measured at proximal, mid and distal segments along compressed (i.e. L5) and intact (i.e. L4 or S1) nerve roots. FA was significantly reduced in compressed nerve roots and MD, AD and RD were significantly elevated in the most proximal segment of the nerve root studied. FA was significantly correlated with electrophysiological measures of root function: minimum F-wave latency and peripheral motor conduction time (PMCT). In addition, FA along the compressed root also correlated with leg pain and depression score. There was also a relationship between RD and anxiety, leg pain and disability score and AD correlated with depression score. Taken together, these data show that DTI metrics are sensitive to nerve root compression in patients with stenosis as a result of age-related lumbar degeneration. Critically, they show that the changes in microstructural integrity along compressed L5 nerve roots are closely related to a number of clinical symptoms associated with the development of chronic pain as well as neurophysiological assessments of motor function. These inherent relationships between nerve root damage and phenotype suggest that the use DTI is a promising method as a way to stratify treatment selection and predict outcomes.

Brain age predicts mortality.

Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, 'brain-predicted age', derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death.

Relationships between the integrity and function of lumbar nerve roots as assessed by diffusion tensor imaging and neurophysiology.

PURPOSE: Diffusion tensor imaging (DTI) has shown promise in the measurement of peripheral nerve integrity, although the optimal way to apply the technique for the study of lumbar spinal nerves is unclear. The aims of this study are to use an improved DTI acquisition to investigate lumbar nerve root integrity and correlate this with functional measures using neurophysiology. METHODS: Twenty healthy volunteers underwent 3 T DTI of the L5/S1 area. Regions of interest were applied to L5 and S1 nerve roots, and DTI metrics (fractional anisotropy, mean, axial and radial diffusivity) were derived. Neurophysiological measures were obtained from muscles innervated by L5/S1 nerves; these included the slope of motor-evoked potential input-output curves, F-wave latency, maximal motor response, and central and peripheral motor conduction times. RESULTS: DTI metrics were similar between the left and right sides and between vertebral levels. Conversely, significant differences in DTI measures were seen along the course of the nerves. Regression analyses revealed that DTI metrics of the L5 nerve correlated with neurophysiological measures from the muscle innervated by it. CONCLUSION: The current findings suggest that DTI has the potential to be used for assessing lumbar spinal nerve integrity and that parameters derived from DTI provide quantitative information which reflects their function.

Patients with chronic dizziness following traumatic head injury typically have multiple diagnoses involving combined peripheral and central vestibular dysfunction.

OBJECTIVE: We hypothesised that chronic vestibular symptoms (CVS) of imbalance and dizziness post-traumatic head injury (THI) may relate to: (i) the occurrence of multiple simultaneous vestibular diagnoses including both peripheral and central vestibular dysfunction in individual patients increasing the chance of missed diagnoses and suboptimal treatment; (ii) an impaired response to vestibular rehabilitation since the central mechanisms that mediate rehabilitation related brain plasticity may themselves be disrupted. METHODS: We report the results of a retrospective analysis of both the comprehensive clinical and vestibular laboratory testing of 20 consecutive THI patients with prominent and persisting vestibular symptoms still present at least 6months post THI. RESULTS: Individual THI patients typically had multiple vestibular diagnoses and unique to this group of vestibular patients, often displayed both peripheral and central vestibular dysfunction. Despite expert neuro-otological management, at two years 20% of patients still had persisting vestibular symptoms. CONCLUSION: In summary, chronic vestibular dysfunction in THI could relate to: (i) the presence of multiple vestibular diagnoses, increasing the risk of 'missed' vestibular diagnoses leading to persisting symptoms; (ii) the impact of brain trauma which may impair brain plasticity mediated repair mechanisms. Apart from alerting physicians to the potential for multiple vestibular diagnoses in THI, future work to identify the specific deficits in brain function mediating poor recovery from post-THI vestibular dysfunction could provide the rationale for developing new therapy for head injury patients whose vestibular symptoms are resistant to treatment.

Functional neuroimaging of visuo-vestibular interaction.

The brain combines visual, vestibular and proprioceptive information to distinguish between self- and world motion. Often these signals are complementary and indicate that the individual is moving or stationary with respect to the surroundings. However, conflicting visual motion and vestibular cues can lead to ambiguous or false sensations of motion. In this study, we used functional magnetic resonance imaging to explore human brain activation when visual and vestibular cues were either complementary or in conflict. We combined a horizontally moving optokinetic stimulus with caloric irrigation of the right ear to produce conditions where the vestibular activation and visual motion indicated the same (congruent) or opposite directions of self-motion (incongruent). Visuo-vestibular conflict was associated with increased activation in a network of brain regions including posterior insular and transverse temporal areas, cerebellar tonsil, cingulate and medial frontal gyri. In the congruent condition, there was increased activation in primary and secondary visual cortex. These findings suggest that when sensory information regarding self-motion is contradictory, there is preferential activation of multisensory vestibular areas to resolve this ambiguity. When cues are congruent, there is a bias towards visual cortical activation. The data support the view that a network of brain areas including the posterior insular cortex may play an important role in integrating and disambiguating visual and vestibular cues.

Cage subsidence after anterior cervical discectomy and fusion using a cage alone or combined with anterior plate fixation.

PURPOSE: To compare the extent of cage subsidence after anterior cervical discectomy and fusion (ACDF) using a cage alone or combined with anterior plate fixation, and to assess the effect of end plate removal on cage subsidence. METHODS: Records of 23 men and 13 women aged 32 to 82 (mean, 54) years who underwent ACDF for 61 levels using the Solis cage alone (n=46) or combined with anterior plate fixation (n=15) were reviewed. The extent of cage subsidence was determined by comparing immediately postoperative (within one week) with final follow-up radiographs. Cage subsidence was defined as the sum subsidence of the superior and inferior part of the cage into the vertebral body. Mild and major cage subsidence was defined as ≤2 mm and >2 mm, respectively. RESULTS: Patients who underwent ACDF using a cage alone or combined with anterior plate fixation were comparable in terms of age, gender, follow-up duration, and number of levels decompressed. Cage subsidence occurred in 33 (54%) of the 61 levels decompressed. In the cage alone group, the extent of cage subsidence was greater (1.68 vs. 0.57 mm, p=0.039) and the rate of major cage subsidence was higher (28% vs. 7%, p=0.08). The inferior part of the cage was more vulnerable to subsidence compared with the superior part (median subsidence: 3.0 vs. 1.4 mm, p<0.0001). Cage subsidence occurred more often when the end plate was removed rather than preserved (58% vs. 18%, p<0.002). CONCLUSION: The extent of cage subsidence was greater after ACDF with cage alone. Cage subsidence occurred more often when the end plate was removed. Additional anterior plate fixation is recommended when the end plate is removed.

A pragmatic randomized controlled trial to evaluate the effectiveness of a facilitated exercise intervention as a treatment for postnatal depression: the PAM-PeRS trial.

BACKGROUND: Postnatal depression affects about 10-15% of women in the year after giving birth. Many women and healthcare professionals would like an effective and accessible non-pharmacological treatment for postnatal depression. METHOD: Women who fulfilled the International Classification of Diseases (ICD)-10 criteria for major depression in the first 6 months postnatally were randomized to receive usual care plus a facilitated exercise intervention or usual care only. The intervention involved two face-to-face consultations and two telephone support calls with a physical activity facilitator over 6 months to support participants to engage in regular exercise. The primary outcome was symptoms of depression using the Edinburgh Postnatal Depression Scale (EPDS) at 6 months post-randomization. Secondary outcomes included EPDS score as a binary variable (recovered and improved) at 6 and 12 months post-randomization. RESULTS: A total of 146 women were potentially eligible and 94 were randomized. Of these, 34% reported thoughts of self-harming at baseline. After adjusting for baseline EPDS, analyses revealed a -2.04 mean difference in EPDS score, favouring the exercise group [95% confidence interval (CI) -4.11 to 0.03, p = 0.05]. When also adjusting for pre-specified demographic variables the effect was larger and statistically significant (mean difference = -2.26, 95% CI -4.36 to -0.16, p = 0.03). Based on EPDS score a larger proportion of the intervention group was recovered (46.5% v. 23.8%, p = 0.03) compared with usual care at 6 months follow-up. CONCLUSIONS: This trial shows that an exercise intervention that involved encouragement to exercise and to seek out social support to exercise may be an effective treatment for women with postnatal depression, including those with thoughts of self-harming.

Sedentary time and markers of inflammation in people with newly diagnosed type 2 diabetes.

BACKGROUND AND AIMS: We investigated whether objectively measured sedentary time was associated with markers of inflammation in adults with newly diagnosed type 2 diabetes. METHODS AND RESULTS: We studied 285 adults (184 men, 101 women, mean age 59.0 ± 9.7) who had been recruited to the Early ACTivity in Diabetes (Early ACTID) randomised controlled trial. C-reactive protein (CRP), adiponectin, soluble intracellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and accelerometer-determined sedentary time and moderate-vigorous physical activity (MVPA) were measured at baseline and after six-months. Linear regression analysis was used to investigate the independent cross-sectional and longitudinal associations of sedentary time with markers of inflammation. At baseline, associations between sedentary time and IL-6 were observed in men and women, an association that was attenuated following adjustment for waist circumference. After 6 months of follow-up, sedentary time was reduced by 0.4 ± 1.2 h per day in women, with the change in sedentary time predicting CRP at follow-up. Every hour decrease in sedentary time between baseline and six-months was associated with 24% (1, 48) lower CRP. No changes in sedentary time between baseline and 6 months were seen in men. CONCLUSIONS: Higher sedentary time is associated with IL-6 in men and women with type 2 diabetes, and reducing sedentary time is associated with improved levels of CRP in women. Interventions to reduce sedentary time may help to reduce inflammation in women with type 2 diabetes.

Cost and effectiveness of treatment options for childhood obesity.

UNLABELLED: What is already known about this subject Approximately one-fifth of children in the UK are obese. There are currently few, effective interventions available in the UK. There are very little data on relative cost-effectiveness of childhood obesity interventions, which hampers the commissioning of future services. What this study adds Simple multi-component obesity interventions can be provided at relatively low cost per 0.1 body mass index standard deviation score (BMI SDS) improvement. More intensive and effective interventions incur greater cost per 0.1 BMI SDS reduction but this may be justified given the improved overall BMI SDS reduction attained. OBJECTIVE: To describe the costs and outcomes of three models of care for childhood obesity previously evaluated in two 2-arm pilot randomized trials in England. The treatments were (i) a hospital clinic (control in both trials), comprising a multidisciplinary team of consultant, dietitian and exercise specialist; (ii) a nurse-led primary care clinic replicating the service provided by the hospital and (iii) an intensive intervention using Mandometer®, a behaviour modification tool aimed at encouraging slower eating and better recognition of satiety. METHOD: Patient-level data on resources used to deliver each intervention were collected during the trials. Apart from the cost of the Mandometer® the majority of cost was staff time, dependent on discipline and grade. Outcome for both trials was body mass index standard deviation score (BMI SDS) measured at 12 months. RESULTS: Cost and outcome data were available for 143 children in total. Cost per child was £1749 (SD £243) in the Mandometer® group, £301 (£76) in the primary care group, and £263 (£88) and £209 (£81) in the hospital groups. Mean reduction in BMI SDS was 0.40 (0.35), 0.17 (0.26), 0.15 (0.25) and 0.14 (0.32), respectively. CONCLUSION: Intensive management using Mandometer® was effective but costly (£432 per 0.1 reduction in BMI SDS) compared to conventional care (range £153-£173). A total of 26% children receiving conventional care achieved a clinically meaningful reduction in BMI SDS; however, use of Mandometer® training may be justified in children not responding to conventional lifestyle interventions.

A pragmatic randomised controlled trial to evaluate the cost-effectiveness of a physical activity intervention as a treatment for depression: the treating depression with physical activity (TREAD) trial.

OBJECTIVE: The TREAting Depression with physical activity (TREAD) study investigated the cost-effectiveness of a physical activity intervention, in addition to usual general practitioner care, as a treatment for people with depression. DESIGN: An individually randomised, pragmatic, multicentre randomised controlled trial with follow-up at 4, 8 and 12 months. A subset of participants took part in a qualitative study that investigated the acceptability and perceived benefits of the intervention. SETTING: General practices in the Bristol and Exeter areas. PARTICIPANTS: Aged 18-69 years with an International Statistical Classification of Diseases and Related Health Problems, 10th Edition (ICD-10) diagnosis of depression and scoring ≥ 14 on the Beck Depression Inventory (BDI). Those who were unable to complete self-administered questionnaires in English, with medical contraindications to physical activity or with psychosis, bipolar disorder or serious drug abuse were excluded. INTERVENTIONS: We devised an intervention designed to encourage choice and autonomy in the adoption of physical activity. It consisted of up to three face-to-face and ten telephone contacts delivered by a trained physical activity facilitator over an 8-month period. MAIN OUTCOME MEASURES: The primary outcome was the BDI score measured at 4 months. Secondary outcomes included depressive symptoms over the 12 months and quality of life, antidepressant use and level of physical activity. RESULTS: The study recruited 361 patients, with 182 randomised to the intervention arm and 179 to the usual care arm; there was 80% retention at the 4-month follow-up. The intervention group had a slightly lower BDI score at 4 months [-0.54, 95% confidence interval (CI) -3.06 to 1.99] but there was no evidence that the intervention improved outcome for depression. Neither was there any evidence to suggest a difference in the prescription of or self-reported use of antidepressants. However, the amount of physical activity undertaken by those who had received the intervention was increased (odds ratio 2.3, 95% CI 1.3 to 3.9) and was sustained beyond the end of the intervention. From a health-care perspective, the intervention group was more costly than the usual care group, with the cost of the intervention £220 per person on average. It is therefore extremely unlikely that the intervention is cost-effective as a treatment for depression using current willingness-to-pay thresholds. CONCLUSIONS: This physical activity intervention is very unlikely to lead to any clinical benefit in terms of depressive symptoms or to be a cost-effective treatment for depression. Previous research has reported some benefit and there are three possible reasons for this discrepancy: first, even though the intervention increased self-reported physical activity, the increase in activity was not sufficiently large to lead to a measurable influence; second, only more vigorous activity might be of benefit; and third, previous studies had recruited individuals with a pre-existing commitment to physical activity. Future research is needed to identify and explain the mechanisms by which depression might be effectively treated, including, in particular, specific guidance on the optimum type, intensity and duration of physical activity required to produce a therapeutic effect. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16900744. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 10. See the HTA programme website for further project information.

Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin.

BACKGROUND: Psilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defences. AIMS: To test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiographical memories under psilocybin and placebo. METHOD: Ten healthy participants received two functional magnetic resonance imaging scans (2 mg intravenous psilocybin v. intravenous saline), separated by approximately 7 days, during which they viewed two different sets of 15 positive autobiographical memory cues. Participants viewed each cue for 6 s and then closed their eyes for 16 s and imagined re-experiencing the event. Activations during this recollection period were compared with an equivalent period of eyes-closed rest. We split the recollection period into an early phase (first 8 s) and a late phase (last 8 s) for analysis. RESULTS: Robust activations to the memories were seen in limbic and striatal regions in the early phase and the medial prefrontal cortex in the late phase in both conditions (P<0.001, whole brain cluster correction), but there were additional visual and other sensory cortical activations in the late phase under psilocybin that were absent under placebo. Ratings of memory vividness and visual imagery were significantly higher after psilocybin (P<0.05) and there was a significant positive correlation between vividness and subjective well-being at follow-up (P<0.01). CONCLUSIONS: Evidence that psilocybin enhances autobiographical recollection implies that it may be useful in psychotherapy either as a tool to facilitate the recall of salient memories or to reverse negative cognitive biases.

Sedentary time, breaks in sedentary time and metabolic variables in people with newly diagnosed type 2 diabetes.

AIMS/HYPOTHESIS: We investigated whether objectively measured sedentary time and interruptions in sedentary time are associated with metabolic factors in people with type 2 diabetes. METHODS: We studied 528 adults (30-80 years) with newly diagnosed type 2 diabetes, who were participants in a diet and physical activity intervention. Waist circumference (WC), fasting HDL-cholesterol, insulin and glucose levels, HOMA of insulin resistance (HOMA-IR) and physical activity (accelerometer) were measured at baseline and at 6 months follow-up. Linear regression models were used to investigate cross-sectional and longitudinal associations of accelerometer-derived sedentary time and breaks in sedentary time (BST) with metabolic variables. RESULTS: In cross-sectional analyses each hour of sedentary time was associated with larger WC (unstandardised regression coefficient [B] [95% CI] 1.89 cm [0.94, 2.83]; p < 0.001), higher insulin (B = 8.22 pmol/l [2.80, 13.65]; p = 0.003) and HOMA-IR (B = 0.42 [0.14, 0.70]; p = 0.004), and lower HDL-cholesterol (B = -0.04 mmol/l [-0.06, -0.01]; p = 0.005). Adjustment for WC attenuated all associations. Each BST was associated with lower WC (B = -0.15 cm [- 0.24, -0.05]; p = 0.003) and there was evidence of a weak linear association with HDL-cholesterol, but no association with insulin levels or HOMA-IR. Volume of sedentary time at baseline predicted HDL-cholesterol (B = -0.05 mmol/l [-0.08, -0.01]; p = 0.007), insulin levels (B = 8.14 pmol/l [0.1.51, 14.78]; p = 0.016) and HOMA-IR (B = 0.49 [0.08, 0.90]; p = 0.020) at 6 months, though not WC. Baseline BST did not substantially predict any metabolic variables at follow-up. No change was seen in sedentary time or BST between baseline and 6 months follow-up. CONCLUSIONS/INTERPRETATION: Higher sedentary time is associated with a poorer metabolic profile in people with type 2 diabetes.

Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: the Early ACTID randomised controlled trial.

BACKGROUND: Lifestyle changes soon after diagnosis might improve outcomes in patients with type 2 diabetes mellitus, but no large trials have compared interventions. We investigated the effects of diet and physical activity on blood pressure and glucose concentrations. METHODS: We did a randomised, controlled trial in southwest England in adults aged 30-80 years in whom type 2 diabetes had been diagnosed 5-8 months previously. Participants were assigned usual care (initial dietary consultation and follow-up every 6 months; control group), an intensive diet intervention (dietary consultation every 3 months with monthly nurse support), or the latter plus a pedometer-based activity programme, in a 2:5:5 ratio. The primary endpoint was improvement in glycated haemoglobin A(1c)(HbA(1c)) concentration and blood pressure at 6 months. Analysis was done by intention to treat. This study is registered, number ISRCTN92162869. FINDINGS: Of 593 eligible individuals, 99 were assigned usual care, 248 the diet regimen, and 246 diet plus activity. Outcome data were available for 587 (99%) and 579 (98%) participants at 6 and 12 months, respectively. At 6 months, glycaemic control had worsened in the control group (mean baseline HbA(1c) percentage 6·72, SD 1·02, and at 6 months 6·86, 1·02) but improved in the diet group (baseline-adjusted difference in percentage of HbA(1c) -0·28%, 95% CI -0·46 to -0·10; p=0·005) and diet plus activity group (-0·33%, -0·51 to -0·14; p<0·001). These differences persisted to 12 months, despite less use of diabetes drugs. Improvements were also seen in bodyweight and insulin resistance between the intervention and control groups. Blood pressure was similar in all groups. INTERPRETATION: An intensive diet intervention soon after diagnosis can improve glycaemic control. The addition of an activity intervention conferred no additional benefit. FUNDING: Diabetes UK and the UK Department of Health.

A pragmatic randomised controlled trial to compare antidepressants with a community-based psychosocial intervention for the treatment of women with postnatal depression: the RESPOND trial.

OBJECTIVES: To evaluate clinical effectiveness at 4 weeks of antidepressant therapy for mothers with postnatal depression (PND) compared with general supportive care; to compare outcome at 18 weeks of those randomised to antidepressant therapy with those randomised to listening visits as the first intervention (both groups were to be allowed to receive the alternative intervention after 4 weeks if the woman or her doctor so decided); and to assess acceptability of antidepressants and listening visits to users and health professionals. DESIGN: A pragmatic two-arm individually randomised controlled trial. SETTING: Participants were recruited from 77 general practices: 21 in Bristol, 21 in south London and 35 in Manchester. PARTICIPANTS: A total of 254 women who fulfilled International Classification of Diseases version 10 criteria for major depression in the first 6 postnatal months were recruited and randomised. INTERVENTIONS: Women were randomised to receive either an antidepressant, usually a selective serotonin reuptake inhibitor prescribed by their general practitioner (GP), or non-directive counselling (listening visits) from a specially trained research health visitor (HV). The trial was designed to compare antidepressants with general supportive care for the first 4 weeks, after which women allocated to listening visits commenced their sessions. It allowed for women to receive the alternative intervention if they had not responded to their allocated intervention or wished to change to, or add in, the alternative intervention at any time after 4 weeks. MAIN OUTCOME MEASURES: The duration of the trial was 18 weeks. Primary outcome, measured at 4 weeks and 18 weeks post randomisation, was the proportion of women improved on the Edinburgh Postnatal Depression Scale (EPDS), that is scoring < 13. Secondary outcomes were the EPDS measured as a continuous variable at 4 and 18 weeks, and scores on various other questionnaires. RESULTS: At 4 weeks, women were more than twice as likely to have improved if they had been randomised to antidepressants compared with listening visits, which started after the 4-week follow-up, i.e. after 4 weeks of general supportive care [primary intention-to-treat (ITT), 45% versus 20%; odds ratio (OR) 3.4, 95% confidence interval (CI) 1.8 to 6.5, p < 0.001]. Explanatory analyses emphasised these findings. At 18 weeks, ITT analysis revealed that the proportion of women improving was 11% greater in the antidepressant group, but logistic regression analysis showed no clear benefit for one group over the other [62% versus 51%, OR 1.5 (95% CI 0.8 to 2.6), p = 0.19]. Overall, there was a difference between the groups in favour of the antidepressant group of about 25 percentage points at 4 weeks, which reduced at 18 weeks. No statistical support existed for a benefit of antidepressants at 18 weeks, but 95% CIs could not rule out a clinically important benefit. It was difficult for GPs not to prescribe antidepressants to women randomised to listening visits after the initial 4 weeks, so many women received both interventions in both groups by 18 weeks and consequently power was reduced. Qualitative interviews with women revealed a preference for listening visits but an acceptance that antidepressants might be necessary. They wished to be reassured that their GP and HV were offering continuity of care focusing on their particular set of circumstances. Interviews with GPs and HVs revealed lack of collaboration in managing care for women with PND; neither professional group was willing to assume responsibility. CONCLUSIONS: At 4 weeks, antidepressants were significantly superior to general supportive care. Trial design meant that by 18 weeks many of the women initially randomised to listening visits were also receiving antidepressants, and more vice versa. The lack of evidence for differences at 18 weeks is likely to reflect a combination of reduced power and the considerable degree of switching across the two interventions. Qualitative study revealed that women found both antidepressants and listening visits effective depending on their circumstances and preferences. The trial indicates that early treatment with antidepressants leads to clinical benefit for women with PND.

Distinct frontal systems for response inhibition, attentional capture, and error processing.

Stopping an action in response to an unexpected event requires both that the event is attended to, and that the action is inhibited. Previous neuroimaging investigations of stopping have failed to adequately separate these cognitive elements. Here we used a version of the widely used Stop Signal Task that controls for the attentional capture of stop signals. This allowed us to fractionate the contributions of frontal regions, including the right inferior frontal gyrus and medial frontal cortex, to attentional capture, response inhibition, and error processing. A ventral attentional system, including the right inferior frontal gyrus, has been shown to respond to unexpected stimuli. In line with this evidence, we reasoned that lateral frontal regions support attentional capture, whereas medial frontal regions, including the presupplementary motor area (pre-SMA), actually inhibit the ongoing action. We tested this hypothesis by contrasting the brain networks associated with the presentation of unexpected stimuli against those associated with outright stopping. Functional MRI images were obtained in 26 healthy volunteers. Successful stopping was associated with activation of the right inferior frontal gyrus, as well as the pre-SMA. However, only activation of the pre-SMA differentiated stopping from a high-level baseline that controlled for attentional capture. As expected, unsuccessful attempts at stopping activated the anterior cingulate cortex. In keeping with work in nonhuman primates these findings demonstrate that successful motor inhibition is specifically associated with pre-SMA activation.

Pathways to the diagnosis of ovarian cancer in the UK: a cohort study in primary care.

OBJECTIVE: To identify the routes patients with ovarian cancer take between first symptom presentation and diagnosis. DESIGN: Cohort study. SETTING: The study took place in 39 general practices in Devon, UK. POPULATION: All ovarian cancer patients identified in the practices, with a diagnosis between 2000 and 2007 inclusive. METHODS: All patients had their cancer symptoms, referrals, and diagnoses identified and dated using their doctors' records. MAIN OUTCOME MEASURES: Numbers of patients taking specific routes to diagnosis, together with the time taken to diagnosis. RESULTS: Three main routes to diagnosis emerged. The first was the expected route of outpatient referral: 195 (92% of the total) had at least one of the seven ovarian cancer symptoms or an abdominal mass. A total of 123 (58%) were referred to a specialist, although only 65 (31%) were referred to a gynaecologist. Thirty-five (17%) were initially investigated within primary care by ultrasound scanning, and a further 35 (17%) were admitted as emergencies. The interval from first symptom to referral was similar across the different pathways, with a median (interquartile range) time between the first symptom presenting to primary care and first investigation or referral being 2.5 (0, 27.5) days. The median interval from first symptom reported in primary care to diagnosis was 74.5 (32, 159) days. CONCLUSIONS: Only a minority of ovarian cancer patients follow the expected route to diagnosis, of urgent referral to a gynaecologist. In most women, GPs rapidly identified the need to investigate. Avoidable delays generally occurred after the decision to investigate was made.

The treatment of non-union of the clavicle with the AO mini external fixator.

Osteosynthesis of non-union of fractures of the clavicle were achieved using bone graft and the AO mini external fixator. The technique was used in nine patients, and no neurovascular or pleural complications occurred. The average time before the patient was considered for this method was 11 months. The external fixator was removed at an average of eight weeks, with solid union in all cases. The outcome was excellent and all patients returned to pre-injury level of normal activity. This method provides safe and relatively simple treatment for this difficult non-union.