Ivor Lewis vs Mckeown esophagectomy: analysis of operative outcomes from the ACS NSQIP database.

OBJECTIVES: Ivor Lewis and McKeown esophagectomy are common techniques to treat esophageal cancer. In this study, we aim to compare these two approaches. METHOD: We used the American College of Surgeons National Surgical Quality Improvement Project database (2005-2017) to compare both techniques using bivariate analysis after propensity matching. RESULTS: We identified 6136 patients with esophagectomy and divided them into 2 groups based on whether they received a McKeown (1676; 27.31%) or an Ivor Lewis (4460; 70.14%) esophagectomy. McKeown esophagectomy was associated with higher rates of superficial surgical site infections (8.02% vs 3.67%, p < 0.001), anastomotic leaks (9.12% vs 7.71%, p = 0.02), prolonged intubation (15.06% vs 10.10%, p < 0.001), re-intubation (15.30% vs 10.34%, p ≤ 0.001), and return to the OR (16.46% vs 11.32%, p < 0.001). The McKeown esophagectomy patients also had longer hospital length of stay (14.5 ± 11.99 vs 13.37 ± 11.8, p = 0.002), higher re-admission rate (21.56% vs 16.87%, p = 0.002), and higher discharges to nursing/rehabilitation institutions (14.06% vs 11.99%, p = 0.004).The mortality rate and positive resection margins were not significantly different. There was a trend toward more utilization of Ivor Lewis esophagectomy over years. CONCLUSION: When compared to Ivor Lewis esophagectomy, McKeown esophagectomy is associated with more unplanned intubation, increased difficulty weaning from the ventilator, incisional surgical site infections, anastomotic leak, and higher length of stay.

Intergenerational transmission of adverse childhood experiences via maternal depression and anxiety and moderation by child sex.

Adverse childhood experiences (ACEs) of parents are associated with a variety of negative health outcomes in offspring. Little is known about the mechanisms by which ACEs are transmitted to the next generation. Given that maternal depression and anxiety are related to ACEs and negatively affect children's behaviour, these exposures may be pathways between maternal ACEs and child psychopathology. Child sex may modify these associations. Our objectives were to determine: (1) the association between ACEs and children's behaviour, (2) whether maternal symptoms of prenatal and postnatal depression and anxiety mediate the relationship between maternal ACEs and children's behaviour, and (3) whether these relationships are moderated by child sex. Pearson correlations and latent path analyses were undertaken using data from 907 children and their mothers enrolled the Alberta Pregnancy Outcomes and Nutrition study. Overall, maternal ACEs were associated with symptoms of anxiety and depression during the perinatal period, and externalizing problems in children. Furthermore, we observed indirect associations between maternal ACEs and children's internalizing and externalizing problems via maternal anxiety and depression. Sex differences were observed, with boys demonstrating greater vulnerability to the indirect effects of maternal ACEs via both anxiety and depression. Findings suggest that maternal mental health may be a mechanism by which maternal early life adversity is transmitted to children, especially boys. Further research is needed to determine if targeted interventions with women who have both high ACEs and mental health problems can prevent or ameliorate the effects of ACEs on children's behavioural psychopathology.

Association of the ROBO1 gene with reading disabilities in a family-based analysis.

Linkage studies have identified a locus on chromosome 3 as reading disabilities (RD) and speech and sound disorder (SSD) susceptibility region, with both RD and SSD sharing similar phonological processing and phonological memory difficulties. One gene in this region, roundabout homolog 1 (ROBO1), has been indicated as a RD candidate and has shown significant association with measures of phonological memory in a population-based sample. In this study, we conducted a family-based association analysis using two independent samples collected in Toronto and Calgary, Canada. Using the two samples, we tested for association between ROBO1 single nucleotide polymorphisms (SNPs) and RD, along with quantitative measures for reading, spelling and phonological memory. One SNP, rs331142, which was selected based on its correlation with ROBO1 expression in brain tissue, was found to be significantly associated with RD in the Toronto sample with over transmission of the minor C allele (P = 0.001), correlated with low expression. This SNP is located ~200 bp from a putative enhancer and results for a marker within the enhancer, rs12495133, showed evidence for association with the same allele in both the Toronto and Calgary samples (P = 0.005 and P = 0.007). These results support previous associations between ROBO1 and RD, as well as correlation with low gene expression, suggesting a possible mechanism of risk conferred by this gene.

A family-based association analysis and meta-analysis of the reading disabilities candidate gene DYX1C1.

Reading disabilities (RD) have a significant genetic basis and have shown linkage to multiple regions including chromosome 15q. Dyslexia susceptibility 1 candidate gene 1 (DYX1C1) on chromosome 15q21 was originally proposed as a candidate gene with two potentially functional polymorphisms at the -3G/A and 1249G/T positions showing association with RD. However, subsequent studies have yielded mixed results. We performed a literature review and meta-analysis of the -3G/A and 1249G/T polymorphisms, including new unpublished data from two family-based samples. Ten markers in DYX1C1 were genotyped in the two independently ascertained samples. Single marker and -3G/A:1249G/T haplotype analyses were performed for RD in both samples, and quantitative trait analyses using standardized reading-related measures was performed in one of the samples. For the meta-analysis, we used a random-effects model to summarize studies that tested for association between -3G/A or 1249G/T and RD. No significant association was found between the DYX1C1 SNPs and RD or any of the reading-related measures tested after correction for the number of tests performed. The previously reported risk haplotype (-3A:1249T) was not biased in transmission. A total of 9 and 10 study samples were included in the meta-analysis of the -3G/A and 1249G/T polymorphisms, respectively. Neither polymorphism reached statistical significance, but the heterogeneity for the 1249G/T polymorphism was high. The results of this study do not provide evidence for association between the putatively functional SNPs -3G/A and 1249G/T and RD.

Dense-map genome scan for dyslexia supports loci at 4q13, 16p12, 17q22; suggests novel locus at 7q36.

Analysis of genetic linkage to dyslexia was performed using 133,165 array-based SNPs genotyped in 718 persons from 101 dyslexia-affected families. Results showed five linkage peaks with lod scores >2.3 (4q13.1, 7q36.1-q36.2, 7q36.3, 16p12.1, and 17q22). Of these five regions, three have been previously implicated in dyslexia (4q13.1, 16p12.1, and 17q22), three have been implicated in attention-deficit hyperactivity disorder (ADHD, which highly co-occurs with dyslexia; 4q13.1, 7q36.3, 16p12.1) and four have been implicated in autism (a condition characterized by language deficits; 7q36.1-q36.2, 7q36.3, 16p12.1, and 17q22). These results highlight the reproducibility of dyslexia linkage signals, even without formally significant lod scores, and suggest dyslexia predisposing genes with relatively major effects and locus heterogeneity. The largest lod score (2.80) occurred at 17q22 within the MSI2 gene, involved in neuronal stem cell lineage proliferation. Interestingly, the 4q13.1 linkage peak (lod 2.34) occurred immediately upstream of the LPHN3 gene, recently reported both linked and associated with ADHD. Separate analyses of larger pedigrees revealed lods >2.3 at 1-3 regions per family; one family showed strong linkage (lod 2.9) to a known dyslexia locus (18p11) not detected in our overall data, demonstrating the value of analyzing single large pedigrees. Association analysis identified no SNPs with genome-wide significance, although a borderline significant SNP (P = 6 × 10(-7)) occurred at 5q35.1 near FGF18, involved in laminar positioning of cortical neurons during development. We conclude that dyslexia genes with relatively major effects exist, are detectable by linkage analysis despite genetic heterogeneity, and show substantial overlapping predisposition with ADHD and autism.

Predictive accuracy of the wide range assessment of memory and learning in children with attention deficit hyperactivity disorder and reading difficulties.

The predictive accuracy of the Wide Range Assessment of Memory and Learning (WRAML; Sheslow & Adams, 1990) over and above more standardized diagnostic tools in children with attention deficit hyperactivity disorder (ADHD) and reading disabilities (RD) was examined. Fifty-three children with ADHD, 63 with RD, 63 with ADHD-RD, and 112 normal comparison children were administered the WRAML, the Wechsler Intelligence Scale for Children-Third Edition (WISC-III; Wechsler, 1991), the Achenbach (1991) Child Behavior Checklist (CBCL), and the Woodcock-Johnson Psycho-Educational Battery-Revised (WJ-R; Woodcock & Johnson, 1989). Results of a series of discriminant function analyses revealed that the academic, intellectual, and behavioral measures could correctly classify 73.1% of children, but the WRAML subtests alone were able to correctly classify only 58.5% of participants. Combining all of the memory, academic, intellectual, and behavioral measures resulted in 77.5% of cases being correctly classified. These results suggest that the use of a measure of memory functioning such as the WRAML did not significantly improve the predictive accuracy of a diagnosis of ADHD, RD, or both over and above more standard diagnostic academic, intellectual, and behavioral measures.

Evidence for a susceptibility locus on chromosome 6q influencing phonological coding dyslexia.

A linkage study of 96 dyslexia families containing at least two affected siblings (totaling 877 individuals) has found evidence for a dyslexia susceptibility gene on chromosome 6q11.2-q12 (assigned the name DYX4). Using a qualitative phonological coding dyslexia (PCD) phenotype (affected, unaffected, or uncertain diagnoses), two-point parametric analyses found highly suggestive evidence for linkage between PCD and markers D6S254, D6S965, D6S280, and D6S251 (LOD(max) scores = 2.4 to 2.8) across an 11 cM region. Multipoint parametric analysis supported linkage of PCD to this region (peak HLOD = 1.6), as did multipoint nonparametric linkage analysis (P = 0.012). Quantitative trait linkage analyses of four reading measures (phonological awareness, phonological coding, spelling, and rapid automatized naming speed) also provided evidence for a dyslexia susceptibility locus on chromosome 6q. Using a variance-component approach, analysis of phonological coding and spelling measures resulted in peak LOD scores at D6S965 of 2.1 and 3.3, respectively, under 2 degrees of freedom. Furthermore, multipoint nonparametric quantitative trait sibpair analyses suggested linkage between the 6q region and phonological awareness, phonological coding, and spelling (P = 0.018, 0.017, 0.0005, respectively, for unweighted sibpairs < 18 years of age). Although conventional significance thresholds were not reached in the linkage analyses, the chromosome 6q11.2-q12 region clearly warrants investigation in other dyslexia family samples to attempt replication and confirmation of a dyslexia susceptibility gene in this region.

The term comorbidity is of questionable value in reference to developmental disorders: data and theory.

Over the last decade, there has been an enormous increase in the number of studies evaluating the overlap of developmental syndromes or disorders in both children and adults. This overlap of symptoms is often referred to as comorbidity, a term we criticize in this article because of its unsubstantiated presumption of independent etiologies. The premise of this article is that discrete categories do not exist in real life, and that it is misleading to refer to overlapping categories or symptoms as "comorbidities." We illustrate our point by presenting data from 179 school-age children evaluated with rigorous research criteria for seven disorders: reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), developmental coordination disorder (DCD), oppositional defiant disorder (ODD), conduct disorder (CD), depression, and anxiety. Fully 50% of this sample met the criteria for at least two diagnoses. The children with ADHD were at higher risk of having at least a second disorder compared to the children with RD. Overall, the high rates of overlap of these behavioral, emotional, and educational deficits in this broadly ascertained sample support the idea that the concept of comorbidity is inadequate. We discuss the concept of atypical brain development as an explanatory idea to interpret the high rate of overlap of developmental disorders.

Effective mood stabilization with a chelated mineral supplement: an open-label trial in bipolar disorder.

BACKGROUND: To determine in open trials the therapeutic benefit of a nutritional supplement for bipolar disorder. METHOD: The sample consisted of 11 patients with DSM-IV-diagnosed bipolar disorder aged 19 to 46 years, who were taking a mean of 2.7 psychotropic medications each at study entry. Three additional patients dropped out prematurely. The intervention is a broad-based nutritional supplement of dietary nutrients, primarily chelated trace minerals and vitamins, administered in high doses. At study entry and periodically thereafter, patients were assessed with the Hamilton Rating Scale for Depression (HAM-D), the Brief Psychiatric Rating Scale (BPRS), and the Young Mania Rating Scale (YMRS). RESULTS: For those who completed the minimum 6-month open trial, symptom reduction ranged from 55% to 66% on the outcome measures; need for psychotropic medications decreased by more than 50%. Paired t tests revealed treatment benefit on all measures for patients completing the trial: HAM-D mean score at entry = 19.0, mean score at last visit = 5.4, t = 5.59, df = 9, p < 01; BPRS mean score at entry = 35.3, mean score at last visit = 7.4, t = 2.57, df = 9, p <.05; YMRS mean score at entry = 15.1, mean score at last visit = 6.0, t = 4.11, df = 9, p < .01. The effect size for the intervention was large (> .80) for each measure. The number of psychotropic medications decreased significantly to a mean +/- SD of 1.0+/-1.1 (t = 3.54, df = 10, p < .01). In some cases, the supplement replaced psychotropic medications and the patients remained well. The only reported side effect (i.e., nausea) was infrequent, minor, and transitory. CONCLUSION: Some cases of bipolar illness may be ameliorated by nutritional supplementation. A randomized, placebo-controlled trial in adults with bipolar I disorder is currently underway, as well as open trials in children.

Atypical brain development: a conceptual framework for understanding developmental learning disabilities.

This article presents ideas that are, in part, a response to the ambiguity in the neurological research on learning disorders, the growing awareness that developmental disabilities are typically nonspecific and heterogeneous, and the growing scientific literature showing that comorbidity of symptoms and syndromes is the rule rather than the exception. This article proposes the term atypical brain development (ABD) as a unifying concept to assist researchers and educators trying to come to terms with these dilemmas. ABD is meant to serve as an integrative concept of etiology, the expression of which is variable within and across individuals. ABD does not itself represent a specific disorder or disease. It is a term that can be used to address the full range of developmental disorders that are found to be overlapping much of the time in any sample of children. Although similar in spirit to the older term of minimal brain dysfunction (MBD), in that it closely links neurology with behavioral difficulties, ABD as proposed here differs in several ways. In support of the ABD conceptual framework, first, we consider the ABD concept in terms of its superiority to the older notion of MBD. Second, we provide a brief review of the burgeoning literature on the overlap of the various developmental disabilities. Third, we review some of the scientific literature that supports the ABD concept. Our sole purpose in proposing this concept is to initiate dialogue and debate on several critical issues across a wide variety disciplines. Hence, this article is not intended to be a definitive statement of a rigid perspective. It reflects neither a nonmalleable philosophical position, nor any type of condemnation of other perspectives. It does, however, reflect a data-based and philosophical trend visible in the field of learning disabilities, as well as the broader area of childhood developmental disorders.

Reliability and validity of a parent questionnaire on childhood motor skills.

OBJECTIVE: As the consequences of clumsiness in children become better understood, the need for valid measurement tools is apparent. Parent report has the potential for providing historical knowledge of the child's motor skills, as well as perceptions of their children's motor difficulties. The objective was to develop a parent questionnaire to identify motor difficulties in children. METHOD: A sample of 306 children participated in the development of a 17-item parent questionnaire, called the Developmental Coordination Disorder Questionnaire (DCDQ). Internal consistency, concurrent and construct validity were examined. RESULTS: The DCDQ proved capable of distinguishing children who had motor problems (as measured by standardized tests) from children without motor problems. Correlations with standardized tests were significant. Two other studies confirmed the construct validity of the DCDQ. Factor analysis revealed four distinct factors, useful in defining the nature of the difficulties. CONCLUSION: The DCDQ is a succinct and useful measure for use by occupational therapists.

Attributions and perceptions of childhood in women with ADHD symptomatology. Attention-Deficit/Hyperactivity Disorder.

Now that it is recognized that Attention-Deficit/Hyperactivity Disorder (ADHD) often persists into adulthood, there are many adults being identified with ADHD who were not diagnosed as children. Individuals identified with ADHD during adulthood may be at risk for maladaptive attributional styles based on the notion that they were exposed to more negative feedback during childhood than adults without identified ADHD. This study examined current attributions and perceptions of childhood of 51 women identified in adulthood with ADHD symptomatology and 51 nonADHD women. Women with ADHD symptomatology had more uncontrollable, stable, and global attributions, reported more dissatisfaction in their childhood parent, peer, and teacher relationships, and felt less in control of negative childhood events as compared with the nonADHD women. Both depression and ADHD contributed significantly to these group differences, suggesting that negative perceptions and attributions are more than reflections of current thinking and mood. ADHD symptomatology also may be an important risk factor for maladaptive attributions.

Absence of significant linkage between phonological coding dyslexia and chromosome 6p23-21.3, as determined by use of quantitative-trait methods: confirmation of qualitative analyses.

We recently reported the absence of significant linkage of phonological coding dyslexia (PCD) to chromosome 6p23-p21.3 in 79 families with at least two affected siblings, even though linkage of dyslexia to this region has been found in four other independent studies. Whereas, in our previous analyses, we used a qualitative (affected, unaffected, or uncertain) PCD phenotype, here we report a reanalysis of linkage to the chromosome 6p region, by use of four quantitative measures of reading disability: phonological awareness, phonological coding, spelling, and rapid-automatized-naming (RAN) speed. The phonological-coding and spelling measures were highly correlated with each other and with the qualitative PCD phenotype, whereas the phonological-awareness and RAN-speed measures were only moderately correlated with the other measures. Using two-point and multipoint quantitative-trait sib-pair linkage analyses and variance-components analyses, we were unable to detect significant evidence for a locus in the 6p23-p21.3 region influencing any of the quantitative reading measures, supporting our previous qualitative linkage results. The most likely explanation for our inability to detect linkage between dyslexia and this region is that families with subtypes of dyslexia linked to this region are underrepresented in our sample, because of either chance or varying ascertainment criteria.

The IQs of children with ADHD are normally distributed.

The purpose of this investigation was to determine whether or not attention-deficit/hyperactivity disorder (ADHD)-when there was an absence of reading problems-was associated with having a high IQ. The vocabulary and block design short forms of the Wechsler Intelligence Scale for Children-Third Edition were administered to 63 children with ADHD, 69 children with reading difficulties (RD), and 68 children with comorbid ADHD + RD. Results indicated that the distributions of estimated Full Scale IQs (FSIQ) for each of the three groups of children did not differ significantly from a normal distribution, with the majority of children (more than 50%) in each group scoring in the average range. The percentage of children with ADHD who scored in the above-average range for FSIQ was not significantly higher than the percentages of children in the other two groups. No significant group differences emerged for estimated FSIQ, vocabulary, or block design. It was concluded that children with ADHD are no more likely to have an above-average IQ than are other children.

Absence of linkage of phonological coding dyslexia to chromosome 6p23-p21.3 in a large family data set.

Previous studies have suggested that a locus predisposing to specific reading disability (dyslexia) resides on chromosome 6p23-p21.3. We investigated 79 families having at least two siblings affected with phonological coding dyslexia, the most common form of reading disability (617 people genotyped, 294 affected), and we tested for linkage with the genetic markers reported to be linked to dyslexia in those studies. No evidence for linkage was found by LOD score analysis or affected-sib-pair methods. However, using the affected-pedigree-member (APM) method, we detected significant evidence for linkage and/or association with some markers when we used published allele frequencies with weighting of rarer alleles. APM results were not significant when we used marker allele frequencies estimated from parents. Furthermore, results were not significant with the more robust SIMIBD method using either published or parental marker frequencies. Finally, family-based association analysis using the AFBAC program showed no evidence for association with any marker. We conclude that the APM method should be used only with extreme caution, because it appears to have generated false-positive results. In summary, using a large data set with high power to detect linkage, we were unable to find evidence for linkage or association between phonological coding dyslexia and chromosome 6p markers.

Absence of an association between IgE-mediated atopic responsiveness and ADHD symptomatology.

There are mixed research results in the literature regarding a possible association between Attention Deficit Hyperactivity Disorder (ADHD) and atopic disorders. If such an association were supported, the implications for underlying pathophysiology would be significant. We evaluated level of atopic responsiveness (based on IgE-mediated response to skin prick tests) in 312 referrals to a pediatric allergist. Based on the atopy code, children were categorized as non-atopic, or moderately or severely atopic. Parents completed the Child Behavior Checklist (CBCL). Univariate analyses on the eight CBCL subscales revealed no differences between the atopic groups. Our results do not support an association between IgE-Mediated atopic responsiveness and ADHD, but they do not rule out an association between allergic symptoms and ADHD based on some other mechanism.