Prevalence of malnutrition in pediatric pulmonary hypertension cohort and role for registered dietitian involvement.

Introduction: Pediatric pulmonary hypertension (PH) is a serious condition with increased risk for malnutrition due to increased caloric needs and reduced energy intake. This combination of disease and dynamic elements make it particularly challenging to meet expected growth patterns. Pediatric PH patients require close monitoring and individualized nutrition interventions to best meet nutrient needs. The prevalence of malnutrition and effective nutrition interventions in pediatric PH has not been studied. Methods: Using our electronic medical record (EMR) patient care dashboard, malnutrition prevalence was assessed by reviewing the active problem list of all active PH patients at our center. A chart review compared patients with diagnosed malnutrition in the EMR to those with malnutrition identified by a registered dietitian (RD) using a standardized tool. Chart reviews also assessed outcomes of RD interventions. Results: 195 patients were identified as active PH patients followed by our PH center during the study period (November 2021 to January 2023). Of these, 5% (10/195) had an ICD-10 code for malnutrition listed in their chart. However, upon further chart review of the remaining 185 patients, 22% (41/185) had malnutrition identified by a RD using Texas Children's Malnutrition Tool, totaling 51/195 (26%) malnourished patients. The PH RD saw 25/51 (49%) patients during PH clinic visits in the study period. At follow up visits (3-4 months after initial assessment), 56% (14/25) patients seen by the PH RD either improved or resolved their malnutrition status by z-score assessment. Conclusion: Malnutrition is present in pediatric PH, although underappreciated and underdiagnosed. Managing malnutrition in pediatric PH requires close monitoring, multidisciplinary involvement, and individualized nutrition recommendations. This is best achieved by a dedicated PH RD who is familiar with the unique needs of this population and available to provide consistent nutritional assessments and interventions to reduce malnutrition in this population.

Complications of haemophilia in babies (first two years of life): a report from the Centers for Disease Control and Prevention Universal Data Collection System.

AIM: To describe the prevalence and complications in babies ≤2 years with haemophilia. METHODS: We used a standardized collection tool to obtain consented data on eligible babies aged ≤2 years with haemophilia enrolled in the Centers for Disease Control and Prevention Universal Data Collection System surveillance project at US Hemophilia Treatment Centers (HTCs). RESULTS: Of 547 babies, 82% had haemophilia A, and 70% were diagnosed within one month of birth. Diagnosis was prompted by known maternal carrier status (40%), positive family history (23%), bleeding (35%) and unknown 2%; 81% bled during the first two years. The most common events were bleeding (circumcision, soft tissue, oral bleeding) and head injury. There were 46 episodes of intracranial haemorrhage (ICH) in 37 babies (7%): 18 spontaneous, 14 delivery related, 11 traumatic, 2 procedure related and 1 unknown cause. Of the 176 central venous access devices (CVADs) in 148 (27%) babies, there were 137 ports, 22 surgically inserted central catheters and 20 peripherally inserted central catheters. Ports had the lowest complication rates. Inhibitors occurred in 109 (20%) babies who experienced higher rates of ICH (14% vs. 5%; P = 0.002), CVAD placement (61% vs. 19%; P < 0.001) and CVAD complications (44% vs. 26%; P < 0.001). The most common replacement therapy was recombinant clotting factor concentrates. CONCLUSION: Bleeding events in haemophilic babies ≤2 years were common; no detectable difference in the rates of ICH by the mode of delivery was noted. Neonatal factor exposure did not affect the inhibitor rates. Minor head trauma, soft tissue and oropharyngeal bleeding were the leading indications for treatment.

Hepatitis B vaccination is effective by subcutaneous route in children with bleeding disorders: a universal data collection database analysis.

Subcutaneous (SQ) vs. intramuscular (IM) vaccination may cause fewer injection site complications in children with bleeding disorders, but little is known about comparative immunogenicity. To compare immunogenicity of hepatitis B virus (HBV) vaccination administered SQ or IM to individuals <2 years old with bleeding disorders, we performed a retrospective analysis of HBV surface antibody titres among patients enrolled in the universal data collection database who had received three doses of HBV vaccine solely by one route (SQ or IM). Data reviewed were from an initial visit before 24 months of age, until time of hepatitis antibody titre testing. The SQ and IM study groups did not differ in demographics, haemophilia type or severity or bleeding history. The mean age at the time of HBV surface antibody (anti-HBs) testing was 56.9 ± 20.3 months. Eighty-five of 92 subjects (92.4%) who received vaccine SQ developed a positive antibody titre (>12 IU/L), compared to 101/114 (88.6%) who received IM (P = 0.30). There was no statistically significant difference in distribution of titre values. The average age of the subjects at time of testing was 53 ± 20 months in the SQ group vs. 60 ± 20 months in the IM group (P = 0.02). The average time between the last dose of vaccine and anti-HBs testing was 47.6 ± 18.5 months among SQ vaccinated subjects vs. 51.6 ± 20.5 months in the IM group (P = 0.2). Immunogenicity to hepatitis B vaccination by the SQ and IM routes is similar.

Increased prevalence of inhibitors in Hispanic patients with severe haemophilia A enrolled in the Universal Data Collection database.

Neutralizing inhibitors develop in 20-30% of patients with severe factor VIII (FVIII) deficiency. It is well established that Blacks have a higher prevalence of inhibitors than Whites. This is the first study to definitively demonstrate increased inhibitor prevalence in the Hispanic population. We compared inhibitor prevalence among various racial and ethnic groups in a cross-sectional analysis of 5651 males with severe haemophilia A that participated in the Universal Data Collection project sponsored by the Centers for Disease Control and Prevention. We used logistic regression analysis to control for potential confounding variables. We assigned as Hispanic those participants who were white and labelled themselves Hispanic. The prevalence of high-titre inhibitors in the Hispanic participants was 24.5% compared to 16.4% for White non-Hispanic patients (OR 1.4, 95% CI 1.1, 1.7). Possibilities as to the underlying cause of increased inhibitor prevalence in minority ethnic populations include polymorphisms in the FVIII molecule, HLA subtypes and differing inflammatory responses. A better understanding may lead to tailored treatment programmes, or other therapies, to decrease or prevent inhibitor development.

Sites of initial bleeding episodes, mode of delivery and age of diagnosis in babies with haemophilia diagnosed before the age of 2 years: a report from The Centers for Disease Control and Prevention's (CDC) Universal Data Collection (UDC) project.

Lack of detailed natural history and outcomes data for neonates and toddlers with haemophilia hampers the provision of optimal management of the disorder. We report an analysis of prospective data collected from 580 neonates and toddlers aged 0-2 years with haemophilia enrolled in the Universal Data Collection (UDC) surveillance project of the Centers for Disease Control and Prevention (CDC). This study focuses on a cohort of babies with haemophilia whose diagnosis was established before the age of two. The mode of delivery, type and severity of haemophilia, onset and timing of haemorrhages, site(s) of bleeding, provision of prophylaxis with coagulation factor replacement therapy, and the role played by the federally funded Haemophilia Treatment Centers (HTC) in the management of these infants with haemophilia were evaluated. Seventy-five per cent of haemophilic infants were diagnosed early, in the first month of life, especially those with a family history or whose mothers were known carriers; infants of maternal carriers were more likely to be delivered by C-section. Involvement of an HTC prior to delivery resulted in avoidance of the use of assisted deliveries with vacuum and forceps. Bleeding from the circumcision site was the most common haemorrhagic complication, followed by intra- and extra-cranial haemorrhages and bleeding from heel stick blood sampling. Eight per cent of the infants were administered factor concentrate within 24 h of birth; more than half were treated to prevent bleeding. This study highlights the significant rate and the sites of initial bleeding unique to very young children with haemophilia and underscores the need for research to identify optimal evidence-based recommendations for their management.

Truncation of the Mll gene in exon 5 by gene targeting leads to early preimplantation lethality of homozygous embryos.

The mixed lineage leukemia gene (MLL) was originally identified through its involvement in reciprocal translocations in leukemias. MLL codes for a large multidomain protein and bears homology to the Drosophila developmental control gene trithorax in two small domains in the amino terminal region, the central zinc finger domain and the carboxy SET domain. Like the Drosophila trx, MLL has also been shown to be a positive regulator of Hox gene expression. We have targeted Mll (the murine homologue of MLL) in exon 5 causing expression of three truncated in-frame Mll transcripts. These transcripts retain all or some of the AT hook motifs and the DMT domain. This mutant allele causes early in vivo preimplantation lethality of homozygous embryos prior to the 2-cell stage. Embryos cultured in vitro progress to the 2-cell stage, but further development is arrested. The heterozygotes exhibit mild skeletal defects as well as defects in some neuroectodermal derivatives.

Impact of facility size and profit status on intermediate outcomes in chronic dialysis patients.

Little information is available regarding the influence of dialysis facility size or profit status on intermediate outcomes in chronic dialysis patients. We have combined data from the Health Care Financing Administration (HCFA) Core Indicators Project; the end-stage renal disease (ESRD) facility survey; and the HCFA On-Line Survey, Certification, and Reporting System to analyze trends in this area. For hemodialysis patients, larger facilities were more likely than smaller facilities to perform dialysis on patients who were younger than 65 years of age, black, or undergoing dialysis 2 years or more (P < 0.001). Nonprofit facilities were more likely to perform dialysis on patients with diabetes mellitus as a cause of ESRD and less likely to perform dialysis on patients with hypertension as a cause of ESRD compared with for-profit units (P < 0.05). By multivariate analysis, larger facility size was modestly associated with a greater Kt/V value and urea reduction ratio, but not with hematocrit or serum albumin values. Facility profit status was not associated with these intermediate outcomes. For peritoneal dialysis patients, there were no significant differences in patient demographics based on facility size. More patients in nonprofit units had been undergoing dialysis 2 or more years than patients in for-profit units (P < 0.05). By univariate analysis, patients in larger facilities were more likely to have an adequacy measure performed than patients from smaller facilities (P < 0.05). There were few substantial differences in intermediate outcomes in chronic dialysis patients based on facility size or profit status.

Dlx5 regulates regional development of the branchial arches and sensory capsules.

We report the generation and analysis of mice homozygous for a targeted deletion of the Dlx5 homeobox gene. Dlx5 mutant mice have multiple defects in craniofacial structures, including their ears, noses, mandibles and calvaria, and die shortly after birth. A subset (28%) exhibit exencephaly. Ectodermal expression of Dlx5 is required for the development of olfactory and otic placode-derived epithelia and surrounding capsules. The nasal capsules are hypoplastic (e.g. lacking turbinates) and, in most cases, the right side is more severely affected than the left. Dorsal otic vesicle derivatives (e. g. semicircular canals and endolymphatic duct) and the surrounding capsule, are more severely affected than ventral (cochlear) structures. Dlx5 is also required in mandibular arch ectomesenchyme, as the proximal mandibular arch skeleton is dysmorphic. Dlx5 may control craniofacial development in part through the regulation of the goosecoid homeobox gene. goosecoid expression is greatly reduced in Dlx5 mutants, and both goosecoid and Dlx5 mutants share a number of similar craniofacial malformations. Dlx5 may perform a general role in skeletal differentiation, as exemplified by hypomineralization within the calvaria. The distinct focal defects within the branchial arches of the Dlx1, Dlx2 and Dlx5 mutants, along with the nested expression of their RNAs, support a model in which these genes have both redundant and unique functions in the regulation of regional patterning of the craniofacial ectomesenchyme.

Role of the Dlx homeobox genes in proximodistal patterning of the branchial arches: mutations of Dlx-1, Dlx-2, and Dlx-1 and -2 alter morphogenesis of proximal skeletal and soft tissue structures derived from the first and second arches.

The Dlx homeobox gene family is expressed in a complex pattern within the embryonic craniofacial ectoderm and ectomesenchyme. A previous study established that Dlx-2 is essential for development of proximal regions of the murine first and second branchial arches. Here we describe the craniofacial phenotype of mice with mutations in Dlx-1 and Dlx-1 and -2. The skeletal and soft tissue analyses of mice with Dlx-1 and Dlx-1 and -2 mutations provide additional evidence that the Dlx genes regulate proximodistal patterning of the branchial arches. This analysis also elucidates distinct and overlapping roles for Dlx-1 and Dlx-2 in craniofacial development. Furthermore, mice lacking both Dlx-1 and -2 have unique abnormalities, including the absence of maxillary molars. Dlx-1 and -2 are expressed in the proximal and distal first and second arches, yet only the proximal regions are abnormal. The nested expression patterns of Dlx-1, -2, -3, -5, and -6 provide evidence for a model that predicts the region-specific requirements for each gene. Finally, the Dlx-2 and Dlx-1 and -2 mutants have ectopic skull components that resemble bones and cartilages found in phylogenetically more primitive vertebrates.

Randomized trial of breast self-examination in Shanghai: methodology and preliminary results.

BACKGROUND: The efficacy of breast self-examination in helping to reduce mortality from breast cancer has not been rigorously demonstrated. PURPOSE: To assess efficacy, a large, randomized trial was initiated in Shanghai, China. METHODS: From October 1989 to October 1991, 267040 current and retired female employees associated with 520 factories in the Shanghai Textile Industry Bureau were randomly assigned on the basis of factory to either a self-examination instruction group (133375 women) or a control group (133665 women). The women were born within the period from 1925 through 1958. Women in the instruction group were given intensive training in breast self-examination, including the use of silicone breast models and personalized instruction, plus two subsequent reinforcement sessions and multiple reminders to practice the technique. Women in the control group were asked to attend training sessions on the prevention of low back pain. All women have been followed for the development of breast diseases and for death from breast cancer. RESULTS: A high level of participation during the first 4-5 years of the trial was documented among women in the instruction group. Randomly sampled women in this group demonstrated greater proficiency in detecting lumps in breast models than did randomly sampled women in the control group. Approximately equal numbers of breast cancers were detected in the two groups (331 in the instruction group and 322 in the control group) through 1994, which is the last year for which case-finding efforts have been completed. The breast cancers detected in the instruction group were not diagnosed at an appreciably earlier stage or smaller size than those in the control group. More benign breast lesions were detected in the instruction group than in the control group (1457 versus 623, respectively), suggesting a higher index of suspicion for women who received training. Cumulative breast cancer mortality rates through 5 years from entry into the study were nearly equivalent for the two groups. CONCLUSIONS: Breast self-examination has not led to a reduction in mortality from breast cancer in this study cohort in the first several years since the trial began. A shift toward the diagnosis of disease at a less advanced stage in women given instruction has also not been demonstrated. Longer follow-up of participants in this trial is required before final assessment can be made of the efficacy of breast self-examination. IMPLICATIONS: At this time, there is insufficient evidence to recommend for or against the teaching of breast self-examination.

Prediction of group membership in developmental dyslexia, attention deficit hyperactivity disorder, and normal controls using brain morphometric analysis of magnetic resonance imaging.

This study explored the utility of using selected brain morphometric indices for predicting group membership for children with developmental dyslexia (n = 10), attention deficit hyperactivity disorder: combined type (n = 10), and a control group (n = 10). Subjects ranged in age from 6.1 to 16 years (M = 10.5 years, SD = 2.8). None of the subjects were diagnosed with mental retardation, nor did any of the subjects have a history of seizure disorder, head trauma, or other neurodevelopmental disorders. WISC-R Full Scale IQ ranged from 87 to 149 (M = 114.4, SD = 13.3) with no significant differences noted between the clinical groups. Six brain regions, as defined by MRI scans, were selected a priori for inclusion in a discriminant function analysis. Reliability of the morphometric measures ranged from 0.94 to 0.97. One significant discriminant function was generated which accounted for about 61.4% of the variance between groups. The predictive discriminant analysis using the six morphometric MRI measurements classified subjects with an overall 60% accuracy with the best accuracy found for the developmental dyslexia and control groups. A predictive discriminant analysis incorporating these six morphometric measures as well as chronological age and FSIQ increased the overall classification accuracy to 87% with the misclassfied subjects assigned to one of the clinical groups. The findings support the presumed neurological basis for many neurodevelopmental disorders. They also underline the importance of including brain morphometric measures in predictive models.

A survey of marketing practices by family practice residency programs.

The purpose of the study reported in this article was to identify marketing practices that are being utilized by family practice residencies in the United States and to differentiate which strategies were felt to be most useful. A survey questionnaire on marketing strategies was mailed to 361 civilian family practice residencies listed in the 1992 Director of Family Practice Residency Programs. A total of 151 questionnaires were returned for a total response rate of 42.1 percent. The results were summarized using descriptive statistics and Chi-square analysis. Family practice residency programs use a number of different strategies to attract patients. The effectiveness of a given program is dependent on local factors, program strengths and the target population desired. The three most useful marketing strategies reported in the survey were HMO listings, emergency department referrals, and patient referrals. The three least effective strategies were health fairs, sports physicals, and school presentations.

Toward a structure of preschool temperament: factor structure of the temperament assessment battery for children.

Much of the research and thinking in the area of childhood temperament has been guided by the structural and measurement model of Thomas, Chess, and colleagues. Recently, researchers have called into question this structural conception and have explored the factor structure of the instruments based on the Thomas and Chess model. A review of the literature indicates that there are few studies at any one age level, and that much of the research is limited by small samples. The results of a large sample factor analysis of parent and teacher ratings of preschool children are reported. A five-factor solution was judged most appropriate for parent ratings, and a three-factor solution seemed most appropriate for teacher ratings. Relations of these factors to the Big Five personality factors found in adult personality research are discussed.

Neurobehavioural consequences of closed head injury in older adults.

This study examined the neurobehavioural effects of closed head injury (CHI) in adults aged 50 years and older. Twenty two mild to moderate CHI patients who were within seven months of the injury were administered measures of language, memory, attention, and executive functioning. Compared with demographically similar normal controls, the patients exhibited significantly poorer functioning on the cognitive domains. Naming and word fluency under timed conditions, verbal and visual memory, and the ability to infer similarities were especially vulnerable. These initial findings indicate that CHI in older adults produces considerable cognitive deficits in the early stages of recovery. Future research should characterise long term outcome and the potential links between head injury and the development of progressive dementia.

The segmental Bauplan of the rostral zone of the head in vertebrates.

Observations in a wide selection of lower vertebrate embryos have confirmed classical descriptions concerning segmentation of the early head mesoderm. The premandibular (PM) segment is seen as the most rostral representative of a continuous rostro-caudal series of condensations in the paraxial mesoderm, luminisations within which are secondary and variable in occurrence and form. The premandibular condensations are typically in continuity across the midline; the confluence, which comes to lie behind Rathke's pouch, marks the site of first mesoderm formation behind the oral membrane. The underlying consistency of pre-otic segmental pattern throughout the vertebrates is frequently obscured by superimposed variation in morphological detail between species, reflecting the dynamic nature of the morphogenetic tissue processes. Luminisation is one such morphogenetic epiphenomenon. Variations in it account for the terminal (Platt's) vesicle and "proboscis pores": such structures cannot therefore be safely used to infer evolutionary homologies. Many previous difficulties facing segmentation theory are explained as the result of failure to take account of the dynamic nature of the responsible morphogenetic events.

Treatment trial of oxiracetam in Alzheimer's disease.

Twenty-four carefully assessed patients with probable Alzheimer's disease were enrolled in a double-blind, placebo-controlled treatment study of oxiracetam, a nootropic agent reported to improve memory performance in patients with dementia. A broad battery of neuropsychological tests failed to reveal any improvement in the treated group or in any treated patient when individual test scores were analyzed. These findings indicate that oxiracetam is ineffective in reducing cognitive impairment due to Alzheimer's disease.

Dysnomia in Alzheimer's disease: an evaluation of neurobehavioral subtypes.

The relative influence of perceptual and semantic features on naming performance was investigated with reference to the neurobehavioral profiles displayed by patients with Alzheimer's disease (AD). Forty-one patients were classified as manifesting a verbal, visual, or global subtype based upon their pattern of neuropsychological functioning. Perceptual characteristics of to-be-named pictures were varied by manipulating the amount of line detail, whereas semantic qualities were varied by altering word frequency norms. All AD subtypes were less accurate than normal elderly controls in naming low frequency pictures. Patients and controls took longer to name low frequency and high complexity pictures, and this effect was comparable across the AD groups. Patients with predominantly visual deficits were significantly slower in naming than controls, and those with verbal impairments made a higher proportion of semantic naming errors when compared to patients displaying visual or severe global impairments. These results suggest that deficits in semantic processing contribute to naming dysfunction in AD, and they highlight the importance of examining dissociations among neurobehavioral subtypes.