Diffusion Tensor Imaging Detects Early Cerebral Cortex Abnormalities in Neuronal Architecture Induced by Bilateral Neonatal Enucleation: An Experimental Model in the Ferret

Diffusion tensor imaging (DTI) is a technique that non-invasively provides quantitative measures of water translational diffusion, including fractional anisotropy (FA), that are sensitive to the shape and orientation of cellular elements, such as axons, dendrites and cell somas. For several neurodevelopmental disorders, histopathological investigations have identified abnormalities in the architecture of pyramidal neurons at early stages of cerebral cortex development. To assess the potential capability of DTI to detect neuromorphological abnormalities within the developing cerebral cortex, we compare changes in cortical FA with changes in neuronal architecture and connectivity induced by bilateral enucleation at postnatal day 7 (BEP7) in ferrets. We show here that the visual callosal pattern in BEP7 ferrets is more irregular and occupies a significantly greater cortical area compared to controls at adulthood. To determine whether development of the cerebral cortex is altered in BEP7 ferrets in a manner detectable by DTI, cortical FA was compared in control and BEP7 animals on postnatal day 31. Visual cortex, but not rostrally adjacent non-visual cortex, exhibits higher FA than control animals, consistent with BEP7 animals possessing axonal and dendritic arbors of reduced complexity than age-matched controls. Subsequent to DTI, Golgi-staining and analysis methods were used to identify regions, restricted to visual areas, in which the orientation distribution of neuronal processes is significantly more concentrated than in control ferrets. Together, these findings suggest that DTI can be of utility for detecting abnormalities associated with neurodevelopmental disorders at early stages of cerebral cortical development, and that the neonatally enucleated ferret is a useful animal model system for systematically assessing the potential of this new diagnostic strategy

Non-specific symptoms as clues to changes in emotional well-being

Background: Somatic symptoms are a common reason for visits to the family physician. The aim of this study was to examine the relation between non-specific symptoms and changes in emotional well-being and the degree to which the physician considers the possibility of mental distress when faced with such patients. Methods: Patients who complained of two or more symptoms including headache, dizziness, fatigue or weakness, palpitations and sleep disorders over one year were identified from the medical records of a random sample of 45 primary care physicians. A control group matched for gender and age was selected from the same population. Emotional well-being was assessed using the MOS-SF 36 in both groups. Results: The study group and the control group each contained 110 patients. Completed MOS questionnaires were obtained from 92 patients, 48 patients with somatic symptoms and 44 controls. Sixty percent of the patients with somatic symptoms experienced decreased emotional well being compared to 25% in the control group (p =0.00005). Symptoms of dizziness, fatigue and sleep disturbances were significantly linked with mental health impairments. Primary care physicians identified only 6 of 29 patients (21%) whose responses revealed functional limitations due to emotional problems as suffering from an emotional disorder and only 6 of 23 patients (26%) with a lack of emotional well being were diagnosed with an emotional disorder. Conclusions: Non-specific somatic symptoms may be clues to changes in emotional well-being. Improved recognition and recording of mental distress among patients who complain of these symptoms may enable better follow up and treatment

Improving mental health outcomes: achieving equity through quality improvement

Objective. To investigate equity of patient outcomes in a psychological therapy service, following increased access achieved by a quality improvement (QI) initiative. Design. Retrospective service evaluation of health outcomes; data analysed by ANOVA, chi-squared and Statistical Process Control. Setting. A psychological therapy service in Westminster, London, UK. Participants. People living in the Borough of Westminster, London, attending the service (from either healthcare professional or self-referral) between February 2009 and May 2012. Intervention(s). Social marketing interventions were used to increase referrals, including the promotion of the service through local media and through existing social networks. Main Outcome Measure(s). (i) Severity of depression on entry using Patient Health Questionnaire-9 (PHQ9). (ii) Changes to severity of depression following treatment (ΔPHQ9). (iii) Changes in attainment of a meaningful improvement in condition assessed by a key performance indicator. Results. Patients from areas of high deprivation entered the service with more severe depression (M = 15.47, SD = 6.75), com-pared with patients from areas of low (M = 13.20, SD = 6.75) and medium (M = 14.44, SD = 6.64) deprivation. Patients in low

Pain Coping Skills Training for Patients Who Catastrophize About Pain Prior to Knee Arthroplasty: A Multisite Randomized Clinical Trial

BACKGROUND: Pain catastrophizing has been identified as a prognostic indicator of poor outcome following knee arthroplasty. Interventions to address pain catastrophizing, to our knowledge, have not been tested in patients undergoing knee arthroplasty. The purpose of this study was to determine whether pain coping skills training in persons with moderate to high pain catastrophizing undergoing knee arthroplasty improves outcomes 12 months postoperatively compared with usual care or arthritis education. METHODS: A multicenter, 3-arm, single-blinded, randomized comparative effectiveness trial was performed involving 5 university-based medical centers in the United States. There were 402 randomized participants. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Scale, measured at baseline, 2 months, 6 months, and 12 months following the surgical procedure. RESULTS: Participants were recruited from January 2013 to June 2016. In 402 participants, 66% were women and the mean age of the participants (and standard deviation) was 63.2 ± 8.0 years. Three hundred and forty-six participants (90% of those who underwent a surgical procedure) completed a 12-month follow-up. All 3 treatment groups had large improvements in 12-month WOMAC pain scores with no significant differences (p > 0.05) among the 3 treatment arms. No differences were found between WOMAC pain scores at 12 months for the pain coping skills and arthritis education groups (adjusted mean difference, 0.3 [95% confidence interval (CI), -0.9 to 1.5]) or between the pain coping and usual-care groups (adjusted mean difference, 0.4 [95% CI, -0.7 to 1.5]). Secondary outcomes also showed no significant differences (p > 0.05) among the 3 groups. CONCLUSIONS: Among adults with pain catastrophizing undergoing knee arthroplasty, cognitive behaviorally based pain coping skills training did not confer pain or functional benefit beyond the large improvements achieved with usual surgical and postoperative care. Future research should develop interventions for the approximately 20% of patients undergoing knee arthroplasty who experience persistent function-limiting pain. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence

Physician-estimated disease severity in patients with chronic heart or lung disease: a cross-sectional analysis

BACKGROUND: We evaluated how well physicians' global estimates of disease severity correspond to more specific physician-rated disease variables as well as patients' self-rated health and other patient variables. METHODS: We analyzed baseline data from 1662 primary care patients with chronic cardiac or pulmonary disease who were enrolled in a longitudinal study of health-related quality of life (HRQoL). Each patient's primary physician rated overall disease severity, estimated the two-year risk of hospitalization and mortality, and reported the use of disease-specific medications, tests, and subspecialty referrals. Patient variables included sociodemographic characteristics, psychosocial factors, self-rated health, and both generic and disease-specific HRQoL. RESULTS: Physicians rated 40% of their patients "about average", 30% "worse", and 30% "better" than the typical patient seen with the specific target disorder. The physician's global estimate of disease severity was strongly associated (P < 0.001) with each of the five more specific elements of physician-rated disease severity, but only marginally associated with patient self-rated health. Multivariable regression identified a set of patient variables that explained 16.4% of the variance in physician-rated disease severity. CONCLUSION: Physicians' global ratings may provide disease severity and prognostic information unique from and complementary to patient self-rated health and HRQoL measures. The elements influencing physician-rated disease severity and its predictive validity for clinical outcomes warrant prospective investigation

Attentional bias for negative expressions depends on previous target location: replicable effect but unreliable measures

Observability of threat-related spatial attentional biases may require previous-trial responses associated with threat-related locations. This carryover effect might affect reliability and correlations. In Study 1, a diagonalized Visual Probe Task was completed online (N=131) with colour, anger, fear and disgust stimuli, with questionnaires on aggression, anxiety, depression and impulsivity. Bias towards negative stimuli was found only following previous targets on the negative location. Study 2 aimed to test an interpretation in terms of cue-evoked attention. Task variants were completed (N=101) with and without removal of the cue when targets appeared. Anger and disgust stimuli and aggression, anxiety and depression scales were used. Carryover was replicated with no interaction with cue offset. Over both tasks, reliability was low and no robust correlations with questionnaires were found. Carryover thus determined whether attentional bias to negative facial expressions was observed, but analyses taking this into account did not improve reliability or reveal correlations

Opioid use prior to knee arthroplasty in patients who catastrophize about their pain: preoperative data from a multisite randomized clinical trial

Background: Opioid use rates prior to knee arthroplasty (KA) among people who catastrophize about their pain are unknown. We determined prevalence of opioid use and compared patterns of preoperative opioid use and oral morphine equivalent (OME), a measure of daily opioid dose, across varied geographic sites. We also determined which baseline variables were associated with opioid use and OME. Patients and methods: Preoperative opioid use data described type of opioid, dosage, and frequency among 397 patients scheduled for KA. Demographic, knee-related pain, and psychological distress dimensions were examined to identify variables associated with opioid use and opioid dose (OME). Opioid use prevalence and OME were compared across the four sites. A three-level censored regression determined variables associated with opioid use and OME. Results: The overall opioid use prevalence was 31.7% (95% confidence interval [CI] = 27.0, 36.3) and varied across sites from 15.9% (95% CI = 9.0, 22.8) to 51.2% (95% CI = 40.5, 61.9). After adjustment, patients using opioids were more likely to be younger, African American, and have higher self-efficacy and comorbidity scores (P < 0.05). The only variable independently associated with OME was lower depressive symptoms (P < 0.05). Conclusion: People who catastrophized prior to KA did not demonstrate increased preoperative opioid use based on current evidence, but variation in the prevalence of opioid use across study sites was substantial. Variables associated with opioid use were non-modifiable demographic and comorbidity variables

Depression and Risk of Sudden Cardiac Death and Coronary Heart Disease in Women Results From the Nurses' Health Study

ObjectivesWe assessed the association between depression and sudden cardiac death (SCD) and cardiac events among individuals without baseline coronary heart disease (CHD).BackgroundDepression is a risk factor for cardiac events and mortality among those with CHD, possibly from arrhythmia.MethodsWe studied depressive symptoms and a proxy variable for clinical depression consisting of severe symptoms and/or antidepressant medication use and their relationship to cardiac events in the Nurses' Health Study. Questionnaires in 1992, 1996, and 2000 assessed symptoms with the Mental Health Index (MHI-5), and antidepressant use was assessed in 1996 and 2000. Primary end points included SCD, fatal CHD, and nonfatal myocardial infarction.ResultsAmong 63,469 women without prior CHD/stroke in 1992, 7.9% had MHI-5 scores <53, previously found to predict clinical depression. Depressive symptoms were associated with CHD events, and the relationship was strongest for fatal CHD, where the association remained significant even after controlling for CHD risk factors (hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.11 to 2.00 for MHI-5 score <53). In models from 1996 onward, our proxy variable for clinical depression was most associated with SCD in multivariable models (HR: 2.33, 95% CI: 1.47 to 3.70), and this risk was primarily due to a specific relationship between antidepressant use and SCD (HR: 3.34, 95% CI: 2.03 to 5.50).ConclusionsIn this cohort of women without baseline CHD, depressive symptoms were associated with fatal CHD, and a measure of clinical depression including antidepressant use was specifically associated with SCD. Although antidepressant use might be a marker of worse depression, its specific association with SCD merits further study