A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency.

BACKGROUND: Combined immunodeficiency (CID) is characterized by severe recurrent infections with normal numbers of T and B lymphocytes but with deficient cellular and humoral immunity. Most cases are sporadic, but autosomal recessive inheritance has been described. In most cases, the cause of CID remains unknown. OBJECTIVE: We wanted to identify the genetic cause of CID in 2 siblings, the products of a first-cousin marriage, who experienced recurrent bacterial and candidal infections with bronchiectasis, growth delay, and early death. METHODS: We performed immunologic, genetic, and biochemical studies in the 2 siblings, their family members, and healthy controls. Reconstitution studies were performed with T cells from mucosa-associated lymphoid tissue lymphoma-translocation gene 1-deficient (Malt1(-/-)) mice. RESULTS: The numbers of circulating T and B lymphocytes were normal, but T-cell proliferation to antigens and antibody responses to vaccination were severely impaired in both patients. Whole genome sequencing of 1 patient and her parents, followed by DNA sequencing of family members and healthy controls, showed the presence in both patients of a homozygous missense mutation in MALT1 that resulted in loss of protein expression. Analysis of T cells that were available on one of the patients showed severely impaired IκBα degradation and IL-2 production after activation, 2 events that depend on MALT1. In contrast to wild-type human MALT1, the patients' MALT1 mutant failed to correct defective nuclear factor-κB activation and IL-2 production in MALT1-deficient mouse T cells. CONCLUSIONS: An autosomal recessive form of CID is associated with homozygous mutations in MALT1. If future patients are found to be similarly affected, they should be considered as candidates for allogeneic hematopoietic cell transplantation.

Anticipatory guidance and early child development: pediatrician advice, parent behaviors, and unmet needs as reported by parents from different backgrounds.

Anticipatory guidance is acknowledged as an important aspect of pediatric practice, and research shows that parents expect and value the information and advice they receive from their pediatric health care providers. This study surveyed 373 parents (88% mothers) of infants in waiting rooms of diverse pediatric practices in Memphis,Tennessee, about their recall of anticipatory guidance received, unmet needs for anticipatory guidance, preferences for sources of information, and activities to promote healthy development. Most parents recalled specific guidance received (diet, communication, and discipline being the most common), and unmet needs (discipline and development being among the most common). Disadvantaged parents reported the fewest unmet needs. Most parents readily named specific activities they engage in to promote development, including reading, educational toys, and nurturing.

Variations in costs for the care of low-birth-weight infants among academic hospitals.

OBJECTIVES: To determine the relative role that academic hospitals (AHs) play in providing neonatal care for low-birth-weight infants within a single state and to determine if there are variations in inpatient costs for neonatal services among AHs. DESIGN: Retrospective analysis of hospital costs for low-birth-weight infants. SETTING: Cases were identified using 2003-2005 data from the Tennessee Hospital Discharge Data System. A specific focus was discharge data from the 5 AHs that support obstetrical residencies and have a neonatal intensive care unit. PARTICIPANTS: Cases included all discharged infants with a birth weight of <2500 grams. RESULTS: The 5 AHs discharged 18% of the total normal-birth-weight infants and 30% of the low-birth-weight infants for the entire state. AHs had higher costs associated with these infants than did other hospitals, with a single exception The difference in costs at this hospital was consistent with the finding of lower utilization rates of hospital services, a shorter average length of stay, and lower costs for infants insured by the state Medicaid program. CONCLUSION: Academic obstetrical hospitals discharged a disproportionately high percentage of low-birth-weight infants compared with other Tennessee hospitals. The lower costs observed in the Shelby County hospital indicates that other hospitals could potentially lower their costs for the care of low-birth-weight infants.

Prevalence and costs of acute and chronic potentially avoidable pediatric hospitalizations in Tennessee.

BACKGROUND: Potentially avoidable pediatric hospitalizations (PAPH) can now be identified using an analytical tool developed by the federal Agency for Healthcare Research and Quality (AHRQ). We apply this new tool to Tennessee inpatient discharge records for 2005 to determine the prevalence of PAPH and analyze the variation patterns of PAPH across racial, gender, and insurance status lines. METHODS: Retrospective analysis of administrative data based on the UB-92 claims forms submitted by all short-term acute-care hospitals in Tennessee for 2005. RESULTS: Tennessee had higher prevalence rates of PAPH than seen in the nation overall for four of the five Ambulatory-Care Sensitive Conditions (ACSC), identified by AHRQ as those hospitalizations which can potentially be avoided. Variations of the rates of PAPH across racial, gender and insurance subgroups were found to mirror those found for pediatric hospitalizations for all conditions. However, when PAPH were grouped according to whether they were chronic or acute in terms of their primary admitting condition, Black children were over-represented in PAPH for chronic conditions such as asthma and diabetes. In addition, Black children's average costs are significantly higher than those for White children irrespective of whether the admitting condition was chronic or acute. CONCLUSIONS: The high rates of PAPH reported in this study imply a weakness in Tennessee's primary care for children. These high rates also point out opportunities for reducing expensive hospitalizations associated with poorly controlled diabetes, asthma exacerbations, and dehydration due to gastroenteritis.

Is environmental tobacco smoke exposure a risk factor for acute gastroenteritis in young children?

Because passive smoke exposure has not been previously linked to diarrhea diseases in children, it was hypothesized that very young children exposed to environmental tobacco smoke (ETS) exposure at home would also be more likely to develop infectious gastroenteritis (GE) than their unexposed counterparts. During 1-year period, 260 children 36 months and younger were prospectively followed up in a private pediatric practice in a southern community in the United States. Multiple logistic regression analysis showed that ETS was strongly predictive of acute GE in the univariate analysis (P = .003). Even after controlling for the various confounders, ETS exposure was still significantly associated with acute GE (relative risk = 2.55; 95% CI = 1.26-5.18). It is speculated that, similar to acute respiratory infections, the same mechanisms may explain why ETS may also be associated with acute infectious GE.

Potentially avoidable pediatric hospitalizations as defined by the Agency for Healthcare Research and Quality: what do they tell us about disparities in child health?

This study was conducted to determine if the Agency for Healthcare Research and Quality's newly established pediatric quality monitors, which measure potentially avoidable hospitalizations, are useful in detecting disparities in health care delivery. Data for all hospital discharges in Tennessee in 2002 were evaluated for the 5 pediatric discharge monitors identified by the Agency for Healthcare Research and Quality. These diagnoses were asthma, short-term complications of diabetes, gastroenteritis, urinary tract infection, and perforated appendix. Black children were more likely to be discharged with the diagnoses of asthma and short-term diabetes complications. Publicly insured children were more likely than commercially insured children to be discharged with each of the 5 potentially avoidable hospitalizations. The results show that black children and children insured by public programs have significantly different discharge rates for pediatric potentially avoidable hospitalizations than do white children or commercially insured children. This could be the result of less access to high-quality ambulatory care.

Do first years really last a lifetime?

Multiple early childhood intervention programs have been introduced to provide at-risk children with a better start in life. This is due to the recognition that early childhood experiences, both positive and negative, can affect the physical, mental, behavioral, and economic well-being of the child. A few of these programs have evaluated long-term outcomes and have demonstrated that the effects of interventions may still be apparent years after the intervention. Pediatricians need to become more aware of the information available about the impact of early childhood events and become more active in promoting proven best intervention practices at the local, state, and national level.

Black/white differential use of health services by young children in a rural Mississippi community.

BACKGROUND AND OBJECTIVES: Use of health services in rural communities has not been well studied. We explored how black and white children used health services in a rural Mississippi community. METHODS: Data were prospectively collected for 396 children attending a private practice to determine if race was associated with the use of health services in this community. RESULTS: White children made more sick contacts than black children (P < 0.001). Black children (36%) were more likely to be treated in the emergency room than white children (24%; P = 0.013). There was no black-white difference in the hospitalization rates, although white children were more likely to undergo ear-nose-throat (ENT) surgery for pressure equalizing tube (PET) placement, and/or tonsillectomy and adenoidectomy (T and A; P < 0.001). Even after controlling for various confounders, the frequency of all physician sick contacts was twice as high for white children than for black children (RR = 2.17; 95% C.I. = 1.32-3.58). CONCLUSION: Overall, black children used disproportionately fewer health services than their white counterparts, but used significantly higher emergency room services. Private insurance coverage was the single most significant variable that accounted for the black-white differential use of the emergency room.

Environmental tobacco smoke exposure: prevalence and mechanisms of causation of infections in children.

BACKGROUND AND OBJECTIVES: Environmental tobacco smoke (ETS) exposure is probably one of the most important public health hazards in our community. Our aim with this article is to (1) review the prevalence of ETS exposure in the United States and how this prevalence is often measured in practice and (2) summarize current thinking concerning the mechanism by which this exposure may cause infections in young children. METHODS: We conducted a Medline search to obtain data published mainly in peer-reviewed journals. RESULTS: There is still a very high prevalence of ETS exposure among US children ranging from 35% to 80% depending on the method of measurement used and the population studied. The mechanism by which ETS may be related to these infections is not entirely clear but may be through suppression or modulation of the immune system, enhancement of bacterial adherence factors, or impairment of the mucociliary apparatus of the respiratory tract, or possibly through enhancement of toxicity of low levels of certain toxins that are not easily detected by conventional means. CONCLUSIONS: The prevalence of ETS exposure in the United States is still very high, and its role in causing infections in children is no longer in doubt even if still poorly understood. Research, therefore, should continue to focus on the various mechanisms of causation of these infections and how to best reduce the exposure levels.