Serum kynurenic acid is reduced in affective psychosis

A subgroup of individuals with mood and psychotic disorders shows evidence of inflammation that leads to activation of the kynurenine pathway and the increased production of neuroactive kynurenine metabolites. Depression is hypothesized to be causally associated with an imbalance in the kynurenine pathway, with an increased metabolism down the 3-hydroxykynurenine (3HK) branch of the pathway leading to increased levels of the neurotoxic metabolite, quinolinic acid (QA), which is a putative Nmethyl- D-aspartate (NMDA) receptor agonist. In contrast, schizophrenia and psychosis are hypothesized to arise from increased metabolism of the NMDA receptor antagonist, kynurenic acid (KynA), leading to hypofunction of GABAergic interneurons, the disinhibition of pyramidal neurons and striatal hyperdopaminergia. Here we present results that challenge the model of excess KynA production in affective psychosis. After rigorous control of potential confounders and multiple testing we find significant reductions in serum KynA and/or KynA/QA in acutely ill inpatients with major depressive disorder (N = 35), bipolar disorder (N = 53) and schizoaffective disorder (N = 40) versus healthy controls (N = 92). No significant difference was found between acutely ill inpatients with schizophrenia (n = 21) and healthy controls. Further, a post hoc comparison of patients divided into the categories of non-psychotic affective disorder, affective psychosis and psychotic disorder (non-affective) showed that the greatest decrease in KynA was in the affective psychosis group relative to the other diagnostic groups. Our results are consistent with reports of elevations in proinflammatory cytokines in psychosis, and preclinical work showing that inflammation upregulates the enzyme, kynurenine mono-oxygenase (KMO), which converts kynurenine into 3-hydroxykynurenine and quinolinic acid

In-hospital outcomes and 30-day readmission rates among ischemic and hemorrhagic stroke patients with delirium

OBJECTIVE: Delirium is associated with poor outcomes among critically ill patients. However, it is not well characterized among patients with ischemic or hemorrhagic stroke (IS and HS). We provide the population-level frequency of in-hospital delirium and assess its association with in-hospital outcomes and with 30-day readmission among IS and HS patients. METHODS: We analyzed Nationwide in-hospital and readmission data for years 2010-2015 and identified stroke patients using ICD-9 codes. Delirium was identified using validated algorithms. Outcomes were in-hospital mortality, length of stay, unfavorable discharge disposition, and 30-day readmission. We used survey design logistic regression methods to provide national estimates of proportions and 95% confidence intervals (CI) for delirium, and odds ratios (OR) for association between delirium and poor outcomes. RESULTS: We identified 3,107,437 stroke discharges of whom 7.45% were coded to have delirium. This proportion significantly increased between 2010 (6.3%) and 2015 (8.7%) (aOR, 95% CI: 1.04, 1.03-1.05). Delirium proportion was higher among HS patients (ICH: 10.0%, SAH: 9.8%) as compared to IS patients (7.0%). Delirious stroke patients had higher in-hospital mortality (12.3% vs. 7.8%), longer in-hospital stay (11.6 days vs. 7.3 days) and a significantly greater adjusted risk of 30-day-readmission (16.7%) as compared to those without delirium (12.2%) (aRR, 95% CI: 1.13, 1.11-1.15). Upon readmission, patients with delirium at initial admission continued to have a longer length of stay (7.7 days vs. 6.6 days) and a higher in-hospital mortality (9.3% vs. 6.4%). CONCLUSION: Delirium identified through claims data in stroke patients is independently associated with poor in-hospital outcomes both at index admission and readmission. Identification and management of delirium among stroke patients provides an opportunity to improve outcomes

The gray matter volume of the amygdala is correlated with the perception of melodic intervals: a voxel-based morphometry study

Music is not simply a series of organized pitches, rhythms, and timbres, it is capable of evoking emotions. In the present study, voxel-based morphometry (VBM) was employed to explore the neural basis that may link music to emotion. To do this, we identified the neuroanatomical correlates of the ability to extract pitch interval size in a music segment (i.e., interval perception) in a large population of healthy young adults (N = 264). Behaviorally, we found that interval perception was correlated with daily emotional experiences, indicating the intrinsic link between music and emotion. Neurally, and as expected, we found that interval perception was positively correlated with the gray matter volume (GMV) of the bilateral temporal cortex. More important, a larger GMV of the bilateral amygdala was associated with better interval perception, suggesting that the amygdala, which is the neural substrate of emotional processing, is also involved in music processing. In sum, our study provides one of first neuroanatomical evidence on the association between the amygdala and music, which contributes to our understanding of exactly how music evokes emotional responses

Reference population for international comparisons and time trend surveillance of preterm delivery proportions in three countries

<p>Abstract</p> <p>Background</p> <p>International comparison and time trend surveillance of preterm delivery rates is complex. New techniques that could facilitate interpretation of such rates are needed.</p> <p>Methods</p> <p>We studied all live births and stillbirths (≥ 28 weeks gestation) registered in the medical birth registers in Sweden, Denmark and Norway from 1995 through 2004. Gestational age was determined by best estimate. A reference population of pregnant women was designed using the following criteria: 1) maternal age 20–35, 2) primiparity, 3) spontaneously conceived pregnancy, 4) singleton pregnancy and 5) mother born in the respective country. National preterm delivery rate, preterm delivery rate in the reference population and rate of spontaneous preterm delivery in the reference population were calculated for each country.</p> <p>Results</p> <p>The total national preterm delivery rate (< 37 completed gestational weeks), increased in both Denmark (5.3% to 6.1%, p < 0.001) and Norway (6.0% to 6.4%, p = 0.006), but remained unchanged in Sweden, during 1995–2004. In Denmark, the preterm delivery rate in the reference population (5.3% to 6.3%, p < 0.001) and the spontaneous preterm delivery rate in the reference population (4.4% to 6.8%, p < 0.001) increased significantly. No similar increase was evident in Norway. In Sweden, rates in the reference population remained stable.</p> <p>Conclusion</p> <p>Reference populations can facilitate overview and thereby explanations for changing preterm delivery rates. The model also permits comparisons over time. This model may in its simplicity prove to be a valuable supplement to assessments of national preterm delivery rates for public health surveillance.</p

The Effect of Water Disinfection By-products on Pregnancy Outcomes in Two Southeastern US Communities

To determine if exposure to DBPs during gestation increases the risk of adverse birth outcomes, specifically term small for gestational age (SGA) birth, preterm birth (PTB), and very PTB (<32 weeks gestation)

Retaining women in a prenatal care randomized controlled trial in Canada: implications for program planning

<p>Abstract</p> <p>Background:</p> <p>Challenges to retention in prenatal care seem to exist under both universal systems of care, as in Canada, and non-universal systems of care, as in the United States. However, among populations being served by a system of publicly funded health care, the barriers are less well understood and universal uptake of prenatal services has not been realized. Determining the characteristics of women who dropped out of a prenatal care randomized controlled trial can help identify those who may need alternate retention and service approaches.</p> <p>Methods:</p> <p>In this study, pregnant women were randomized to: a) current standard of care; b) 'a' plus nursing support; or c) 'b' plus a paraprofessional home visitor. 16% of 2,015 women did not complete all three telephone interviews (197 dropped out and 124 became unreachable). Responders were compared to non-responders on demographics, lifestyle, psychosocial factors, and life events using chi-squared tests. Logistic regression models were constructed using stepwise logistic regression to determine the probability of not completing the prenatal program.</p> <p>Results:</p> <p>Completion rates did not differ by intervention. In comparison to responders, non-responders were more likely to be younger, less educated, have lower incomes, smoke, have low social support, have a history of depression, and have separated or divorced parents (all p < 0.05). Unreachable women were more likely to be single, use drugs, report distress and adverse life events (all p < 0.05). Non-Caucasian women were more likely to drop out (p = 0.002). Logistic regression modeling indicated that independent key risk factors for dropping out were: less than high school education, separated or divorced parents, lower social support, and being non-Caucasian. Pregnant women who were single/separated/divorced, less than 25 years old, had less than high school education, earned less than $40,000 in annual household income, and/or smoked had greater odds of becoming unreachable at some point during pregnancy and not completing the study.</p> <p>Conclusion:</p> <p>Women at risk due to lifestyle and challenging circumstances were difficult to retain in a prenatal care study, regardless of the intervention. For women with complex health, lifestyle and social issues, lack of retention may reflect incongruence between their needs and the program.</p> <p>Trial registration:</p> <p>Current Controlled Trials ISRCTN64070727</p

Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma?:Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12-13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies

Association of Silica Exposure with Anti-Neutrophil Cytoplasmic Autoantibody Small-Vessel Vasculitis: A Population-Based, Case-Control Study

Anti-neutrophil cytoplasmic autoantibodies (ANCA) are associated with a category of small-vessel vasculitis (SVV) with frequent glomerulonephritis. The goal of this study was to evaluate the association of lifetime silica exposure with development of ANCA-SVV, with particular attention to exposure dosage, intensity, and time since last exposure. A southeastern United States, population-based, case-control study was conducted. Case patients had ANCA-SVV with pauci-immune crescentic glomerulonephritis. Population-based control subjects were frequency-matched to case patients by age, gender, and state. Jobs were assessed in a telephone interview. Silica exposure scores incorporated exposure duration, intensity, and probability for each job and then were categorized as none, low/medium, or high lifetime exposure. Logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Silica exposure was found in 78 (60%) of 129 case patients and in 49 (45%) of 109 control subjects. There was no increased risk for disease from low/medium exposure relative to no exposure (OR 1.0; 95% CI 0.4 to 2.2) but increased risk with high exposure (OR 1.9; 95% CI 1.0 to 3.5; P = 0.05). Crop harvesting was associated with elevated risk (OR 2.5; 95% CI 1.1 to 5.4; P = 0.03). However, both agricultural and traditional occupational sources contributed to the cumulative silica exposure scores; therefore, the overall effect could not be attributed to agricultural exposures alone. There was no evidence of decreasing by duration of time since last exposure. High lifetime silica exposure was associated with ANCA-SVV. Exposure to silica from specific farming tasks related to harvesting may be of particular importance in the southeastern United States. Interval of time since last exposure did not influence development of ANCA-SVV