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Among patients with schizophrenia (SZ) and bipolar I disorder (BD-I) treated with second-generation antipsychotics (SGAs), clinically-significant weight gain (CSWG) and treatment interruptions (TIs) are challenges that may result in morbidity/mortality.
CSWG and TIs were assessed among patients who initiated oral SGAs of moderate-to-high weight gain risk (no exposure to index SGAs/first-generation antipsychotics for =12 months) using medical records/claims (OM1 Data Cloud; January 2013-February 2020). Outcomes included CSWG (=7% increase in baseline weight) and TIs (switches [to SGAs of low weight gain risk/long-acting injectables] or discontinuations [no SGAs for >30 days]). Descriptive analyses included proportions of patients with CSWG and TIs, and median time to these outcomes.
Approximately three-quarters of patients were overweight/obese at baseline (SZ: N=8,174; BD-I: N=9,142). Within 3 months of SGA initiation, 12% of all patients experienced CSWG. For patients on treatment with index SGAs for >6 months (SZ: 29%; BD-I: 27%), 28% (SZ) and 30% (BD-I) experienced CSWG during follow-up. Median time to CSWG was 14 weeks. CSWG results were numerically similar among patients with SZ and BD-I.
Over 96% of patients had TIs during follow-up (median time of 12 [SZ] and 13 [BD-I] weeks). Among patients with CSWG and subsequent TIs and weight measurements, 74% did not return to baseline weight after interrupting treatment; the remainder returned to baseline weight with median times of 38 (SZ) and 39 (BD-I) weeks. Results suggest that most patients with CSWG do not return to baseline weight after stopping treatment with oral SGAs of moderate-to-high weight gain risk.
Limited to no literature exists on the association among sleep quality, obesity and depression in pediatric populations. This study aims to explore this association by examining the sleep quality of children and adolescents before and after a twelve-week comprehensive multidisciplinary pediatric obesity program.
Archival data from the pediatric obesity program included 71 children ages 6-17 (M=10.24, SD=2.74 ) who had been assessed pre and post intervention using the Children's Depression Inventory (CDI), a Sleep Questionnaire, and physician derived Body Mass Index (BMI). On all measures, higher scores indicate presence of symptoms of depression, sleep difficulties, or obesity.
High scores on the CDI proved to predict poor sleep quality both at intake and exit. Hierarchical regression exhibited change in BMI from intake to exit and predicted sleep quality. As BMI decreased from intake to exit, sleep quality increased.
The current study suggests that sleep quality is influenced by the level of depression in children and adolescents both at pre and post intervention measures. Both depression and BMI influenced sleep quality. When the effect of BMI was accounted for, depression significantly predicted sleep quality. The more depressed children/adolescents reported to be, the lower their quality of sleep. Thus, this study suggests the importance of sleep and depression in the treatment of pediatric obesity. This research supports the importance of a multidisciplinary approach to addressing pediatric obesity.
This paper describes a tri-trophic analysis of the ecological dynamics of a crop, an insect pest, and a natural enemy of the insect pest. Worldwide wheat (Triticum Linnaeus) (Poaceae) production in 2018–2019 was estimated at over 700 million metric tons in 2018–2019. Wheat midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae), a serious insect pest of wheat, is widely distributed in many parts of the world where wheat production occurs. Macroglenes penetrans (Kirby) (Hymenoptera: Pteromalidae), a parasitoid of S. mosellana, has successfully established in most wheat midge-infested areas. Mechanistic, or process-based, population models were used in this study to assess the interactive population dynamics of the three species, based on their respective life cycles and meteorological factors. The models were validated with survey data from multiple sites over numerous years (1991–2016). These simulation models helped to detail our understanding of the tri-trophic population dynamics and will help guide pest management decisions both prior to the growing season and until wheat heading, when wheat is no longer susceptible to S. mosellana. The associated models also help identify gaps in system knowledge, provide a foundation for evaluating future innovative management options, and evaluate the potential impact of a changing climate.
The study investigated antioxidant effects of Se on resilience to diquat-induced oxidative stress in nursery pigs. Thirty-five weaned pigs were individually housed and randomly assigned to one of the five treatments. Pigs were (1) fed a basal diet and intraperitoneally injected with sterile saline (negative control), (2) fed the basal diet and injected with diquat solution (positive control, PC), or fed the basal diet supplemented with 0·3 mg Se/kg as (3) sodium selenite (SS), (4) soyabean protein-chelated Se (SC) or (5) selenised yeast (SY) and intraperitoneally injected with diquat. Pigs were fed the experimental diets for 17 d and injected with diquat at 10 mg/kg body weight or saline on the 11th day of the study (day 0 post-injection (PI)). Diquat exposure induced acute stress and innate immune activation (P < 0·05) at 6 h PI and compromised (P < 0·05) plasma glutathione peroxidase activity on day 2 PI, which was accompanied by an increase in plasma malondialdehyde at 6 h and day 2 PI (P < 0·10). Organic Se, particularly SY, enhanced (P < 0·05) endogenous antioxidant activity in various aspects compared with the PC group. The growth rate and feed intake from day 0 to day 7 PI were significantly lower in the PC, SS and SC groups than the NC group (P < 0·05). Untargeted metabolomics analysis revealed that twenty-two hepatic metabolites (false discovery rate < 0·15) associated with lipid and cellular antioxidant metabolism were altered by diquat. SY restored hepatic metabolic profiles in some but not all samples.
As Bulgaria transitions away from Global Fund grant, robust estimates of the comparative impact of the various response strategies under consideration are needed to ensure sustained effectiveness of the tuberculosis (TB) programme. We tailored an established mathematical model for TB control to the epidemic in Bulgaria to project the likely outcomes of seven intervention scenarios. Under existing programmatic conditions projected forward, the country's targets for achieving TB elimination in the coming decades will not be achieved. No interventions under consideration were predicted to accelerate the baseline projected reduction in epidemiological indicators significantly. Discontinuation of the ‘Open Doors’ program and activities of non-governmental organisations would result in a marked exacerbation of the epidemic (increasing incidence in 2035 by 6–8% relative to baseline conditions projected forward). Changing to a short course regimen for multidrug-resistant TB (MDR-TB) would substantially decrease MDR-TB mortality (by 21.6% in 2035 relative to baseline conditions projected forward). Changing to ambulatory care for eligible patients would not affect TB burden but would be markedly cost-saving. In conclusion, Bulgaria faces important challenges in transitioning to a primarily domestically-financed TB programme. The country should consider maintaining currently effective programs and shifting towards ambulatory care to ensure program sustainability.
Flaviviruses include many viruses causing encephalitis, including West Nile encephalitis, St. Louis encephalitis, tick-borne encephalitis and Japanese encephalitis. Human pegivirus genotype-1 (HPgV-1) is a lesser known member of the Flaviviridae family and has been identified in human serum, cerebrospinal fluid and brain tissue. Here, we describe two adult patients with fatal HPgV-1-associated encephalitis. Neuroimaging revealed multifocal lesions, initially present in the periventricular and brain stem white matter, then one year later throughout the corona radiata bilaterally with marked involvement of the brainstem and cervical spinal cord. Phylogenetic analyses of HPgV-1 showed clustering of brain-derived sequences from both patients with other human pegiviruses. In both patients, a novel 87-nucleotide deletion in the viral NS2 gene was detected. The presence of positive and negative strand HPgV-1 RNA and viral antigens in both patients indicated viral persistence and replication in the CNS. Autopsy showed lymphocyte infiltration and gliosis predominantly in white matter of the brain and brain stem but, to a lesser extent, also in grey matter. Immunofluorescence revealed HPgV-1 NS5A antigen in lymphocytes as well as in astrocytes and oligodendrocytes. Thus, we hypothesize that the novel deletion in the NS2 coding region may have caused HPgV-1 neuroadaptation or might represent a yet unrecognized genotype of human pegivirus.
This presentation will enable the learner to:
1. Describe the clinical and neuropathological features of fatal human pegivirus-associated encephalitis
2. Recognize the importance of molecular analysis in encephalitis cases with unknown etiology
Culturally linked family influences during adolescence are important predictors of health and well-being for Latino youth, yet few studies have examined whether these familial influences are associated with indicators of typical physiological stress processes. Following a cultural neurobiology framework, we examined the role of family in the everyday lives of Latino adolescents (N = 209; Mage = 18.10; 85.1% Mexican descent; 64.4% female) by investigating familism values and perceptions of parent support as well as daily family assistance behaviors in relation to hypothalamic–pituitary–adrenal axis diurnal patterns, indexed by salivary cortisol five times a day for 3 weekdays. Three-level growth curve analyses revealed that perceptions of parental support were associated with greater cortisol awakening responses, whereas familism values were not associated with diurnal cortisol patterns. In day-to-day analyses, assisting family during the day (compared to not assisting family) was associated with lower waking cortisol levels and flatter diurnal slopes the next day. Our findings highlight the dynamic associations and multiple time courses between cultural values and behaviors, daily experiences, and physiological stress processes for Latino adolescents. Further, we identified important cultural risk and promotive factors associated with physiological regulation in daily life and potential pathways toward health outcomes in adulthood.
We performed a systematic review and meta-analyses of studies assessing tuberculosis (TB) patient-related risk factors for transmission of Mycobacterium tuberculosis infection. Meta-analyses were conducted for sputum smear-positivity, lung cavitation and HIV seropositivity of index patients with both crude and adjusted odds ratios (AORs) pooled using random effect models. Thirty-seven studies were included in the review. We found that demographic characteristics such as age and sex were not significant risk factors, while behaviours such as smoking and alcohol intake were associated with infectiousness although inconsistently. Treatment delay of >28 days was a significant predictor of greater infectiousness. Contacts of sputum smear-positive index patients were found to be more likely to be infected than contacts of sputum smear-negative patients, with a pooled AOR of 2.15 (95% confidence interval (CI) 1.47–3.17, I2 = 38%). Similarly, contacts of patients with the cavitary disease were around twice as likely to be infected as contacts of patients without cavitation (pooled AOR 1.9, 95% CI 1.26–2.84, I2 = 63%). In contrast, HIV seropositive patients were associated with few contact infections than HIV seronegative patients (AOR 0.45, 95% CI 0.26–0.80, I2 = 52%). In conclusion, behavioural and clinical characteristics of TB patients can be used to identify highly infectious patients for targeted interventions.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Introduction: In 2008 British Columbia created a nurse (RN) staffed telephone triage service, (TTS) to provide timely advice to non-911 callers (811). A perception exists that some callers are inappropriately directed to emergency departments (EDs) thereby worsening crowding. We sought to determine whether supplementary emergency physician (EP) triage would decrease ED visits while preserving caller safety and satisfaction. Methods: TTS RNs use computer algorithms and judgment to triage callers. Potentially sick callers are directed to “seek care now” (red calls). Often this is to an ED depending on acuity and time of day. In the Vancouver Health Region from April-September 2016 between 8:00-24:00 hours, a co-located EP also spoke with “red” callers to provide further guidance. Callers were followed up with 1 week and satisfaction was evaluated on a 5-point Likert scale. The TTS data was linked to the regional ED database to assess ED attendance within 7 days, and the provincial vital statistics database for 30-day mortality. Our primary outcome was the proportion of unique “red” callers who did not attend the ED compared with a historical cohort one year earlier without EP triage in place. Secondary outcomes were the proportion of “red” callers advised not to attend the ED but (a) attended, (b) admitted, or (c) died. Results: In the study period there were 5105 “red” calls of which 3440 were transferred to the EP (67.4%), 2958 of EP assessed callers (86.0%) had a family doctor, but only one-quarter of such patients could contact their family doctor. Overall, 2301/3440 “red” callers did not attend an ED (67.0%) compared to 2508/4770 in the control period (52.6%), for an absolute reduction of 14.4% (95% CI 12.2 to 16.4%, p<0.0001). In callers for those <17 years old there was a 20.3% (95% CI 16.5 to 24.1%) reduction in ED visits compared to the control group: 771/1520 (50.7%) vs 364/1067 (30.4%). 40% of callers attending an ED (458/1139) were advised to try non-ED follow up by the MD and 108 (9.5%) were admitted, with no difference in 30-day mortality between groups. Age and CTAS distribution were similar between the two groups and the non MD-transferred cohort. Mean caller satisfaction was excellent (4.7/5.0). Conclusion: EP supplementation of a RN advice service has the potential to reduce ED visits by almost 15% while providing excellent safety and satisfaction.
Introduction: Data regarding adverse events (AEs) (unintended harm to the patient from health care provided) among children seen in the emergency department (ED) are scarce despite the high risk setting and population. The objective of our study was to estimate the risk and type of AEs, and their preventability and severity, among children treated in pediatric EDs. Methods: Our prospective cohort study enrolled children <18 years of age presenting for care during 21 randomized 8 hr-shifts at 9 pediatric EDs from Nov 2014 to October 2015. Exclusion criteria included unavailability for follow-up or insurmountable language barrier. RAs collected demographic, medical history, ED course, and systems level data. At day 7, 14, and 21 a RA administered a structured telephone interview to all patients to identify flagged outcomes (e.g. repeat ED visits, worsening/new symptoms, etc). A validated trigger tool was used to screen admitted patients’ health records. For any patients with a flagged outcome or trigger, 3 ED physicians independently determined if an AE occurred. Primary outcome was the proportion of patients with an AE related to ED care within 3 weeks of their ED visit. Results: We enrolled 6377 (72.0%) of 8855 eligible patients; 545 (8.5%) were lost to follow-up. Median age was 4.4 years (range 3 months to 17.9 yrs). Eight hundred and seventy seven (13.8%) were triaged as CTAS 1 or 2, 2638 (41.4%) as CTAS 3, and 2839 (44.7%) as CTAS 4 or 5. Top entrance complaints were fever (11.2%) and cough (8.8%). Flagged outcomes/triggers were identified for 2047 (32.1%) patients. While 252 (4.0%) patients suffered at least one AE within 3 weeks of ED visit, 163 (2.6%) suffered an AE related to ED care. In total, patients suffered 286 AEs, most (67.9%) being preventable. The most common AE types were management issues (32.5%) and procedural complications (21.9%). The need for a medical intervention (33.9%) and another ED visit (33.9%) were the most frequent clinical consequences. In univariate analysis, older age, chronic conditions, hospital admission, initial location in high acuity area of the ED, having >1 ED MD or a consultant involved in care, (all p<0.001) and longer length of stay (p<0.01) were associated with AEs. Conclusion: While our multicentre study found a lower risk of AEs among pediatric ED patients than reported among pediatric inpatients and adult ED patients, a high proportion of these AEs were preventable.
Norovirus (NV) is an important cause of acute gastroenteritis in children, but is also frequently detected in asymptomatic children, which complicates the interpretation of NV detection results in both the clinical setting and population prevalence studies. A total of 807 faecal samples from children aged <5 years hospitalized for acute gastroenteritis were collected in Thai Binh, Vietnam, from January 2011 to September 2012. Real-time RT–PCR was used to detect and quantify NV-RNA in clinical samples. A bimodal distribution of cycle threshold (Ct) values was observed in which the lower peak was assumed to represent cases for which NV was the causal agent of diarrhoea, whereas the higher peak was assumed to represent cases involving an alternative pathogen other than NV. Under these assumptions, we applied finite-mixture modelling to estimate a threshold of Ct <21·36 (95% confidence interval 20·29–22·46) to distinguish NV-positive patients for which NV was the likely cause of diarrhoea. We evaluated the validity of the threshold through comparisons with NV antigen ELISA results, and comparisons of Ct values in patients co-infected with rotavirus. We conclude that the use of an appropriate cut-off value in the interpretation of NV real-time RT–PCR results may improve differential diagnosis of enteric infections, and could contribute to improved estimates of the burden of NV disease.
Multidrug-resistant bacteria are major causes of nosocomial infections and are associated with considerable morbidity, mortality, and healthcare costs. Preventive strategies have therefore become increasingly important. Mathematical modeling has been widely used to understand the transmission dynamics of nosocomial infections and the quantitative effects of infection control measures. This review will explore the principles of mathematical modeling used in nosocomial infections and discuss the effectiveness of infection control measures investigated using mathematical modeling.
Infect Control Hosp Epidemiol 2014;35(12):1521–1530
Nitrous oxide reductase (N2OR), the enzyme responsible for the reduction of N2O to N2 in denitrification, uses copper (Cu) as its cofactor. Its activity is lowered under conditions of Cu deficiency. In general, high organic matter (OM) soil decreases Cu availability. The present study investigated different Cu forms, namely organic (ORG) v. inorganic (INO), and associated concentrations (750, 550, 125, 60 μg Cu/g soil) for their efficacy in affecting denitrification and especially N2OR activity in high OM peat soil in a water saturated anaerobic condition for 24 h. Gas and liquid samples were taken every 8 h and analyzed for NO3−, NO2−, N2O and N2. Inorganic Cu treatments did not affect N transformation rates and N2OR activity among the different treatments (P > 0.05) throughout the incubation compared with the control (CON). The ORG Cu treatments increased NO3− (P < 0.05), NO2− (P < 0.05) and N2O (P < 0.05) transformation rates compared with CON. These changes were ORG Cu dose dependent. N2OR activity increased first in the 750 μg ORG Cu treatment (P < 0.05) during 8 to 16 h followed by the other ORG Cu treatments (P < 0.05) during 16 to 24 h compared with CON. These results highlight the importance of Cu form and concentration on N transformation rate during denitrification. The findings can potentially be applied to systems like soil, wastewater, constructed wetlands, etc., in which reactions of the denitrification pathway are manipulated.
This study explored whether remote blast-related MTBI and/or current Axis I psychopathology contribute to neuropsychological outcomes among OEF/OIF veterans with varied combat histories. OEF/OIF veterans underwent structured interviews to evaluate history of blast-related MTBI and psychopathology and were assigned to MTBI (n = 18), Axis I (n = 24), Co-morbid MTBI/Axis I (n = 34), or post-deployment control (n = 28) groups. A main effect for Axis I diagnosis on overall neuropsychological performance was identified (F(3,100) = 4.81; p = .004), with large effect sizes noted for the Axis I only (d = .98) and Co-morbid MTBI/Axis I (d = .95) groups relative to the control group. The latter groups demonstrated primary limitations on measures of learning/memory and processing speed. The MTBI only group demonstrated performances that were not significantly different from the remaining three groups. These findings suggest that a remote history of blast-related MTBI does not contribute to objective cognitive impairment in the late stage of injury. Impairments, when present, are subtle and most likely attributable to PTSD and other psychological conditions. Implications for clinical neuropsychologists and future research are discussed. (JINS, 2012, 18, 1–11)
The cortisol awakening response (CAR) has been shown to predict major depressive episodes (MDEs) over a 1-year period. It is unknown whether this effect: (a) is stable over longer periods of time; (b) is independent of prospective stressful life events; and (c) differentially predicts first onsets or recurrences of MDEs.
A total of 270 older adolescents (mean age 17.06 years at cortisol measurement) from the larger prospective Northwestern-UCLA Youth Emotion Project completed baseline diagnostic and life stress interviews, questionnaires, and a 3-day cortisol sampling protocol measuring the CAR and diurnal rhythm, as well as up to four annual follow-up interviews of diagnoses and life stress.
Non-proportional person-month survival analyses revealed that higher levels of the baseline CAR significantly predict MDEs for 2.5 years following cortisol measurement. However, the strength of prediction of depressive episodes significantly decays over time, with the CAR no longer significantly predicting MDEs after 2.5 years. Elevations in the CAR did not significantly increase vulnerability to prospective major stressful life events. They did, however, predict MDE recurrences more strongly than first onsets.
These results suggest that a high CAR represents a time-limited risk factor for onsets of MDEs, which increases risk for depression independently of future major stressful life events. Possible explanations for the stronger effect of the CAR for predicting MDE recurrences than first onsets are discussed.
Altered functioning of the hypothalamic–pituitary–adrenal (HPA) axis is a robust correlate of major depression in adults, and to a lesser extent, in adolescents. Premorbid differences in HPA axis function have been found to prospectively predict the onset of adolescent depression. To what extent might our knowledge of HPA axis function in adolescents with, or at risk for, depression, help guide efforts to prevent depression in this age group? We review evidence regarding the role of the HPA axis in the development of adolescent depression, and examine whether and which HPA axis measures might be useful in guiding prevention efforts as (a) as a criterion by which to select youth at risk for depression, (b) as a predictor of which youth will be most responsive to prevention efforts, and (c) as an indicator of whether prevention/intervention efforts are working. We conclude that our current understanding of the HPA axis, and its measurement, in adolescent depression are not sufficiently precise to be of immediate practical use in improving prevention efforts. Incorporating HPA axis measures into prevention studies, however, would be immensely useful in clarifying the role of the HPA axis in adolescent depression, such that future prevention efforts might more confidently rely on HPA axis information.
Thin films of Sr2TiO4 were grown using pulsed laser deposition (PLD) and laser-MBE on -SrTiO3single crystal substrates. Films grown by standard PLD display only a single peak in the X-ray diffraction spectra, corresponding to the (006) peak of the K2NiF4 parent structure. Using a Laser-MBE, controlled two-dimensional growth and RHEED intensity oscillations can be routinely obtained. The period of the RHEED intensity oscillations was confirmed to correspond to the deposition of one-half the unit cell. In contrast to PLD-grown films, the (004) and (006) peaks are observed in XRD spectra for the Laser-MBE-grown films. The intensity of the (004) peak is discussed and modeled with respect to in-plane disorder arising from substrate step-edges and out-of-plane film-substrate structural mismatches. That a single, half unit-cell can be deposited allows one to "flip" the terminating surface of SrTiO3 in a controlled and simple manner from a pure TiO2 layer to a SrO layer. Experimental evidence of the importance of such surface control is given for the SrCuO2 structural stability.
Uniform layers of porous silicon have been produced in a photoelectrochemical etch that show intensity enhancements of up to 100 fold, relative to samples etched in the dark. These films can also show fine structure in their photoluminescence (PL) spectra characteristic of longitudinal optical cavity modes. The highly luminescent, uniform porous layer is generated by illumination with blue or green light during the electrochemical etch of singlecrystal (B-doped) Si, and the enhancement is attributed to a localized photochemical etch process. The relevance of the increased PL intensity and interference-induced spectral changes to measurements of the intrinsic emission spectrum of porous Si are discussed.
Cryptands and crown ethers increase the cation transport in phosphazene and alkoxyaluminate polyelectrolytes. Vibrational spectroscopy indicates that the increased conductivity originates from reduced ion pairing.