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Describing our institution’s off-label use of gabapentin to treat irritability after superior cavopulmonary connection surgery and its impact on subsequent opiate and benzodiazepine requirements.
Methods:
This is a single-center retrospective cohort study including infants who underwent superior cavopulmonary connection operation between 2011 and 2019.
Results:
Gabapentin was administered in 74 subjects (74/323, 22.9%) during the observation period, with a median (IQR) starting dose of 5.7 (3.3, 15.0) mg/kg/day and a maximum dose of 10.7 (5.5, 23.4) mg/kg/day. Infants who underwent surgery in 2015–19 were more likely to receive gabapentin compared with those who underwent surgery in 2011–14 (p < 0.0001). Infants prescribed gabapentin were younger at surgery (137 versus 146 days, p = 0.007) and had longer chest tube durations (1.8 versus 0.9 days, p < 0.001), as well as longer postoperative intensive care (5.8 versus 3.1 days, p < 0.0001) and hospital (11.5 versus 7.0 days, p < 0.0001) lengths of stays. The year of surgery was the only predisposing factor associated with gabapentin administration in multivariate analysis. In adjusted linear regression, infants prescribed gabapentin on postoperative day 0–4 (n = 64) had reduced benzodiazepine exposure in the following 3 days (−0.29 mg/kg, 95% CI −0.52 – −0.06, p = 0.01) compared with those not prescribed gabapentin, while no difference was seen in opioid exposure (p = 0.59).
Conclusions:
Gabapentin was used with increasing frequency during the study period. There was a modest reduction in benzodiazepine requirements associated with gabapentin administration and no reduction in opioid requirements. A randomised controlled trial could better assess gabapentin’s benefits postoperatively in children with congenital heart disease.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
$270 \,\mathrm{deg}^2$
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
$\mu\mathrm{Jy\ beam}^{-1}$
rms at a spatial resolution of
$\sim$
11–18 arcsec, resulting in a catalogue of
$\sim$
220 000 sources, of which
$\sim$
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Method:
Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
Results:
When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
Conclusions:
The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.
Aims
To determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis.
Method
We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum.
Results
Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD.
Conclusions
Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.
Declaration of interest
D.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck.
Objectives: Human immunodeficiency virus (HIV) disproportionately affects Hispanics/Latinos in the United States, yet little is known about neurocognitive impairment (NCI) in this group. We compared the rates of NCI in large well-characterized samples of HIV-infected (HIV+) Latinos and (non-Latino) Whites, and examined HIV-associated NCI among subgroups of Latinos. Methods: Participants included English-speaking HIV+ adults assessed at six U.S. medical centers (194 Latinos, 600 Whites). For overall group, age: M=42.65 years, SD=8.93; 86% male; education: M=13.17, SD=2.73; 54% had acquired immunodeficiency syndrome. NCI was assessed with a comprehensive test battery with normative corrections for age, education and gender. Covariates examined included HIV-disease characteristics, comorbidities, and genetic ancestry. Results: Compared with Whites, Latinos had higher rates of global NCI (42% vs. 54%), and domain NCI in executive function, learning, recall, working memory, and processing speed. Latinos also fared worse than Whites on current and historical HIV-disease characteristics, and nadir CD4 partially mediated ethnic differences in NCI. Yet, Latinos continued to have more global NCI [odds ratio (OR)=1.59; 95% confidence interval (CI)=1.13–2.23; p<.01] after adjusting for significant covariates. Higher rates of global NCI were observed with Puerto Rican (n=60; 71%) versus Mexican (n=79, 44%) origin/descent; this disparity persisted in models adjusting for significant covariates (OR=2.40; CI=1.11–5.29; p=.03). Conclusions: HIV+ Latinos, especially of Puerto Rican (vs. Mexican) origin/descent had increased rates of NCI compared with Whites. Differences in rates of NCI were not completely explained by worse HIV-disease characteristics, neurocognitive comorbidities, or genetic ancestry. Future studies should explore culturally relevant psychosocial, biomedical, and genetic factors that might explain these disparities and inform the development of targeted interventions. (JINS, 2018, 24, 163–175)
Both qualitative and quantitative research routinely fall short, producing misleading causal inferences. Because these weaknesses are in part different, we are convinced that multimethod strategies are productive. Each approach can provide additional leverage that helps address shortcomings of the other. This position is quite distinct from that of Beck, who believes that the two types of analysis cannot be adjoined. We review examples of adjoining that Beck dismisses, based on what we see as his outdated view of qualitative methods. By contrast, we show that these examples demonstrate how qualitative and quantitative analysis can work together.
The discussion of qualitative and quantitative research methods in political science has followed a “long arc of development,” according to Andrew Bennett (this symposium). He sees our book Rethinking Social Inquiry: Diverse Tools, Standards (RSI) as a “key turning point” in this development and as contributing to a more pluralistic vision of methodology. We would certainly be gratified if we have indeed made this contribution. Yet this is an ongoing discussion, and this symposium points to fruitful directions this discussion can take.
Concerns about nutrient loads into our waters have focused attention onpoultry litter applications. Like many states with a large poultry industry,Georgia recently designed a subsidy program to facilitate the transportationof poultry litter out of vulnerable watersheds. This paper uses atransportation model to examine the necessity of a poultry litter subsidy toachieve water protection goals in Georgia. We also demonstrate therelationship between diesel and synthetic fertilizer prices and the value ofpoultry litter. Results suggest that a well-functioning market would be ableto remove excess litter from vulnerable watersheds in the absence of asubsidy.
David A. Freedman presents here a definitive synthesis of his approach to causal inference in the social sciences. He explores the foundations and limitations of statistical modeling, illustrating basic arguments with examples from political science, public policy, law, and epidemiology. Freedman maintains that many new technical approaches to statistical modeling constitute not progress, but regress. Instead, he advocates a 'shoe leather' methodology, which exploits natural variation to mitigate confounding and relies on intimate knowledge of the subject matter to develop meticulous research designs and eliminate rival explanations. When Freedman first enunciated this position, he was met with scepticism, in part because it was hard to believe that a mathematical statistician of his stature would favor 'low-tech' approaches. But the tide is turning. Many social scientists now agree that statistical technique cannot substitute for good research design and subject matter knowledge. This book offers an integrated presentation of Freedman's views.
The goals, prospects and methods of the Prospective Twin Registry in Southwestern China (TRiSC) are described. The aim of this study is to measure children's behavioral development and psychopathology from phenotypic, genetic and environmental perspectives. It focuses on measuring children's behavior and psychopathology from child self-reports, as well as parental and teacher informant reports, and relating it to the children's general cognitive abilities, and to the parenting style in the family. Other variables of interest such as children's temperament and parental health status are discussed, as well as plans for further research.
Process tracing is a fundamental tool of qualitative analysis. This method is often invoked by scholars who carry out within-case analysis based on qualitative data, yet frequently it is neither adequately understood nor rigorously applied. This deficit motivates this article, which offers a new framework for carrying out process tracing. The reformulation integrates discussions of process tracing and causal-process observations, gives greater attention to description as a key contribution, and emphasizes the causal sequence in which process-tracing observations can be situated. In the current period of major innovation in quantitative tools for causal inference, this reformulation is part of a wider, parallel effort to achieve greater systematization of qualitative methods. A key point here is that these methods can add inferential leverage that is often lacking in quantitative analysis. This article is accompanied by online teaching exercises, focused on four examples from American politics, two from comparative politics, three from international relations, and one from public health/epidemiology.
Recent genome-wide association studies in schizophrenia have provided strongest evidence for association and this strengthened when the affected phenotype included bipolar disorder suggesting that genes may not always associate with operationalised diagnostic entities. Several further large Genome Wide Association (GWA) studies on schizophrenia are under way and identified and replicated further loci in well-powered cohorts. The last 2 years have also witnessed an explosion of interest in human Copy Number Variants (CNVs). Deletions recently identified in schizophrenia (1q21.1; 2p16.3; 15q11.2; 15q13.3) have also been most recently found in further neurodevelopmental diseases. Thus, a significant fraction of individuals with neurodevelopmental diseases including schizophrenia carry CNVs and many will be defined as “genomic disorders” in the coming years. These findings could represent a decisive step towards understanding the causes of this severe mental disorder as well as developing new potential treatments. There is new hope that these new avenues will help understanding the neurobiology of schizophrenia in more depth leading to the development of new innovative diagnostic tools and therapies as was the case after the discovery of rare APP and presenilin 1 and 2 mutations in Alzheimer's disease.
The eating disorders anorexia and bulimia nervosa have traditionally been regarded as entirely separate from obesity. Eating disorders have been regarded as Western culture-bound syndromes, arising in societies with excessive emphasis on weight, shape and appearance, and best treated by psychological therapies, in particular cognitive behavioural therapy or familybased interventions. In contrast, obesity has been considered a medical illness with metabolic and genetic origins, and thought to be best treated by mainstream medicine, involving dietary, drug or surgical treatment. We believe that this polarisation is fundamentally flawed, and research and treatment of both types of disorder would be better served by greater appreciation of the psychosocial components of obesity and the biological and genetic components of eating disorders. There are similarities in phenotype (such as excessive attempts at weight control, binge eating behaviours) and in risk factors (such as low self-esteem, external locus of control, childhood abuse and neglect, dieting, media exposure, body image dissatisfaction, weight-related teasing and shared susceptibility genes). One example of shared genetic risk is the brain-derived neurotrophic factor (BNDF) gene, in which the valine allele of the Va166Met amino acid polymorphism predisposes to obesity, whereas the methionine allele predisposes to eating disorders. Thus the evidence suggests that these disorders will have both shared and distinct susceptibility factors; some will predispose to both types of disorder, some will push in opposite directions, and some will separate them.
Abstract. Proportional-hazards models are frequently used to analyze data from randomized controlled trials. This is a mistake. Randomization does not justify the models, which are rarely informative. Simpler methods work better. This discussion is salient because the misuse of survival analysis has introduced a new hazard in epidemiology: It can lead to serious mistakes in medical treatment. Life tables, Kaplan-Meier curves, and proportional-hazards models, aka “Cox models,” all require strong assumptions, such as stationarity of mortality and independence of competing risks. Where the assumptions fail, the methods also tend to fail. Justifying those assumptions is fraught with difficulty. This is illustrated with examples: the impact of religious feelings on survival and the efficacy of hormone replacement therapy. What are the implications for statistical practice? With observational studies, the models could help disentangle causal relations if the assumptions behind the models can be justified.
In this chapter, I will discuss life tables and Kaplan-Meier estimators, which are similar to life tables. Then I turn to proportional-hazards models, aka “Cox models.” Along the way, I will look at the efficacy of screening for lung cancer, the impact of negative religious feelings on survival, and the efficacy of hormone replacement therapy.
What are the conclusions about statistical practice? Proportional-hazards models are frequently used to analyze data from randomized controlled trials.