Correction: Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions.

The original version of this Article contained an error in the spelling of the author N. T. Leach, which was incorrectly given as N. L. Leach. This has been corrected in both the PDF and HTML versions of the Article.

Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions.

PURPOSE: To compare the pattern of gene-specific involvement and the spectrum of variants observed in prenatal and postnatal (mean ± SD, 8.9 ± 9.4 years) cohorts tested for Noonan syndrome and related conditions. METHODS: Outcomes of sequencing panel testing were compared between prenatal (n = 845) and postnatal (n = 409) cohorts. RESULTS: PTPN11 and SOS1 harbored the majority of observed variants in both prenatal and postnatal cohorts, and BRAF, HRAS, KRAS, MAP2K1, MAP2K2, RAF1, and SHOC2 had similarities in their pattern of involvement in both cohorts. PTPN11 was the largest contributor of pathogenic variants and had the lowest frequency of variants of uncertain significance (VUS). SOS1 had the highest VUS frequency in both cohorts. The overall VUS frequency was twice as high in prenatal specimens (58.1 vs. 29.3%). PTPN11 and SOS1 had a 1.5-fold higher VUS frequency in the prenatal cohort (10.7 vs. 7.4% and 95 vs. 61.1%, respectively). The diagnostic yield was 3.7% for prenatal samples, with a higher yield of 12.3% in fetuses with cystic hygroma as a sole finding, and 21.3% for postnatal. CONCLUSION: Comparison of prenatal versus postnatal specimens demonstrates that the pattern of specific gene involvement is similar, whereas the classification spectrum of observed variants differs considerably.

Preventing childhood lead poisoning: the challenge of change.

Because of their rapid growth, immature biologic systems, and their developmental characteristics, children are uniquely vulnerable to exposure to environmental hazards. One of these is lead. Revised lead screening guidelines, published by the Centers for Disease Control and Prevention in Fall 1997, no longer advocate universal screening in some places. These guidelines will (1) require new policies from local public health agencies, (2) require new approaches for clinicians and managed care organizations, especially those with Medicaid-recipient enrollees, to conduct screening of children who may be at risk for exposure to lead, (3) offer new challenges for environmental follow-up to children identified with elevated lead levels, and (4) provide opportunities for collaboration between managed care and public health agencies.

Lead poisoning: low rates of screening and high prevalence among children seen in inner-city emergency departments.

Of 254 children who were 1 to 6 years of age and were tested at two major inner-city emergency departments, 65% had no record of previous lead screening in the previous 30 months, and 71% (97/137) and 50% (58/117), respectively, had blood lead levels > or = 0.48 mumol/L (10 micrograms/dl). The emergency department may be an appropriate resource for lead screening of selected inner-city children.

Effect of HIV infection and tuberculosis on hospitalizations and cost of care for young adults in the United States, 1985 to 1990.

OBJECTIVE: To evaluate the effect of human immunodeficiency virus (HIV) infection and tuberculosis on hospitalizations and the cost of care. DESIGN: National Hospital Discharge Survey, a nationally representative survey of discharges from U.S. nonfederal short-stay hospitals, and statewide billing information. PATIENTS: Patients 15 to 44 years of age with a listed diagnosis of HIV infection (n = 418,200) or active tuberculosis (n = 77,700) during 1985-1990. RESULTS: During 1985-1990, hospitalizations related to HIV infection increased sixfold, from 18 to 102 per 100,000 persons; during 1988-1990, hospitalizations related to tuberculosis increased twofold, from 8 to 16 per 100,000 persons. The prevalence of tuberculosis among HIV-infected patients increased from 2.4% in 1985-1988 to 5.1% in 1989-1990 (P = 0.003). The prevalence of HIV infection among patients with tuberculosis increased from 11% in 1985-1988 to 28% in 1989 to 39% in 1990 (P < 0.001). Infection with HIV was more prevalent among patients with extrapulmonary tuberculosis (31%) than among those with pulmonary tuberculosis (18%) (P = 0.01). An increase in the duration of hospital stay was associated with both tuberculosis and HIV infection. From 1985 to 1990, inpatient care costs increased 7.7-fold and 3.2-fold for HIV and tuberculosis hospitalizations, respectively. During this period, HIV and tuberculosis hospitalizations resulted in 5,793,000 and 1,107,900 days of care, respectively, with an estimated direct cost of $5.7 to $7.4 billion and $0.89 to $1.07 billion, respectively. Estimated national costs of inpatient care for HIV infection or tuberculosis or both totaled $6.4 to $8.1 billion, 5% of which was for patients with both HIV infection and tuberculosis. CONCLUSIONS: This is the first study to use a nationally representative sample of hospitals, combined with cost data, to estimate hospitalizations and their costs for HIV and tuberculosis care. Our findings suggest that the convergence of the HIV and tuberculosis epidemics has had an increasing effect on morbidity and the cost of care among young adults in the United States. The increasing prevalence of comorbidity of HIV infection and tuberculosis in inpatients underscores the need for strict infection control of tuberculosis on the part of hospitals, increased attention to prevention, and early identification and treatment of HIV infection, and tuberculosis to reduce morbidity, hospitalizations, and the cost of care.

Projections of the number of persons diagnosed with AIDS and the number of immunosuppressed HIV-infected persons--United States, 1992-1994.

This report presents projections of the number of persons who will initially be diagnosed with a condition included in the 1987 surveillance definition for acquired immunodeficiency syndrome (AIDS) in the United States during the period 1992-1994. The report also presents estimates and projections of the prevalence of persons infected with the human immunodeficiency virus (HIV) who have CD4+ T-lymphocyte (T-cell) counts < 200/microL and who have not been diagnosed with a condition listed in the 1987 AIDS surveillance definition. These estimates and projections are used to predict the effect of expanding the AIDS surveillance definition to include all HIV-infected persons with a CD4+ T-cell count < 200/microL. Approximately 58,000 persons were diagnosed with AIDS in the United States during 1991. During the period 1992-1994, the number of persons newly diagnosed with AIDS is expected to increase by at most a few percent annually, with approximately 60,000-70,000 persons diagnosed per year. Although AIDS diagnoses among homosexual and bisexual men and among injecting drug users are projected to reach a plateau during this period, the number of AIDS diagnoses among persons whose HIV infection is attributed to heterosexual transmission of HIV is likely to continue to increase through 1994. The number of living persons who have been diagnosed with AIDS is expected to increase from approximately 90,000 in January 1992 to approximately 120,000 in January 1995. There is, however, considerable uncertainty in these projections. For example, the plausible range for the number of persons initially diagnosed with AIDS in 1994 is 43,000-93,000. CDC estimates that, as of January 1992, 115,000-170,000 U.S. residents had severe immunosuppression (a CD4+ T-cell count < 200 cells/microL without a diagnosis of AIDS in an HIV-infected person). Only about 50,000 of these persons were receiving medical care for HIV-related conditions and were known to have a CD4+ T-cell count < 200 cells/microL. The number of persons with severe immunosuppression is expected to increase to 130,000-205,000 by January 1995, with the actual number more likely to be in the lower half of this range than the upper half. The expanded AIDS surveillance definition, which includes severe immunosuppression, is predicted to result in an increase of approximately 75% in the number of persons reported during 1993, but an increase of < 20% in 1994 compared with the number of persons who would have been reported had the definition not been changed.(ABSTRACT TRUNCATED AT 400 WORDS)

Increasing impact of HIV infection on hospitalizations in the United States, 1983-1988.

During 1983-1988, hospitalizations of patients with a diagnosis of human immunodeficiency virus (HIV) infection increased from 1.3 to 33.7 per 100,000 persons. We used the National Hospital Discharge Survey, which is based on a representative sample of discharges from nonfederal short-stay hospitals, to describe illnesses among hospitalized patients with HIV infection. Of 222,200 such hospitalizations during 1983-1988, most occurred among persons who were 25-44 years of age (79%), white (66%), and male (90%). Among men 25-44 years of age, HIV admissions increased from 8.5 to 148.6 per 100,000 persons during 1983-1988; among black men 25-44 years of age, HIV hospitalizations increased from 43.1 to 387.4 per 100,000 persons. Among women, hospitalizations increased 3.4-fold. Frequently listed illnesses in the Centers for Disease Control (CDC) AIDS case definition were Pneumocystis carinii pneumonia (30%), candidiasis (20%), and Kaposi's sarcoma (13%). Other frequently listed illnesses included infections (39%) such as pneumonia, sepsis, and urinary tract infections; blood dyscrasias (30%) such as anemia, thrombocytopenia, and agranulocytosis; metabolic (17%), gastrointestinal (16%), and respiratory disorders (12%); and drug abuse (9%). These data provide a minimum estimate of HIV hospitalizations because for some patients HIV infection may not be specified on the discharge record. HIV hospitalizations are increasing markedly and are associated with a broad spectrum of severe morbidity.

Hepatitis A outbreak in a neonatal intensive care unit: risk factors for transmission and evidence of prolonged viral excretion among preterm infants.

An outbreak of hepatitis A virus (HAV) infection in a neonatal intensive care unit (NICU) provided the opportunity to examine the duration of HAV excretion in infants and the mechanisms by which HAV epidemics are propagated in NICUs. The outbreak affected 13 NICU infants (20%), 22 NICU nurses (24%), 8 other staff caring for NICU infants, and 4 household contacts; 2 seropositive infants (primary cases) received blood transfusions from a donor with HAV infection. Risk factors for infection among nurses were care for a primary infant-case (relative risk [RR], 3.2), drinking beverages in the unit (odds ratio [OR], infinity), and not wearing gloves when taping an intravenous line (OR, 13.7). Among infants, risk factors were care by a nurse who cared for a primary infant-case during the same shift (RR, 6.1). Serial stool samples from infant-cases were tested for HAV antigen (HAV-Ag) by enzyme immunoassay and HAV RNA by nucleic acid amplification using the polymerase chain reaction. Infant-cases excreted HAV-Ag (n = 2) and HAV RNA (n = 3) 4-5 months after they were identified as being infected. Breaks in infection control procedures and possibly prolonged HAV shedding in infants propagated the epidemic in a critical care setting.

A multifocal outbreak of hepatitis A traced to commercially distributed lettuce.

From February 1 through March 20, 1988, 202 cases of hepatitis A were reported in and around Jefferson County, Kentucky. The epidemic curve indicated a common-source exposure. However, there was no apparent single source of exposure from a restaurant, or community gathering; nor was there a geographic clustering by residence. Cases were mainly adults 20-59 years old (89 percent); 51 percent were female. A case-control study using neighborhood controls found that factors associated with hepatitis A were: having eaten downtown (odds ratio [OR] = 4.0) and having dined at any one of three restaurants (OR = 21.0). Case-control studies of patrons of two of these restaurants found that eating green salad was strongly associated with acquiring hepatitis A: OR = 11.6 and OR = 4.4. The three implicated restaurants accounted for 71 percent of the cases. All three restaurants were supplied by the same fresh produce distributor; however, investigation suggested that contamination most likely occurred prior to local distribution. This outbreak of hepatitis A is the first in the United States apparently associated with fresh produce contaminated before distribution to restaurants, and raises important public health issues regarding the regulation of fresh produce.

Heterosexual transmission of hepatitis B virus in Belle Glade, Florida. Belle Glade Study Group.

A population-based serosurvey of human immunodeficiency virus in Belle Glade, FL, enabled evaluation of risk factors for hepatitis B virus (HBV) infection in this racially mixed community. Serum samples from 725 adults and 130 children were tested for markers of HBV infection, and histories of exposure to HBV were obtained by interview. The overall prevalence of past or present HBV infection was 26%; prevalence was 9% among whites, 5% among Hispanics, 30% among blacks, and 57% among Haitians. Prevalence of HBV infection was 3% in children aged 2-10 years and increased to 31% in adults greater than 17 years. Of adults seropositive for HBV, only 5% had homosexual partners or used parenteral drugs, but 47% had a positive serologic test for syphilis. Factors associated with HBV infection in adults were positive serologic test for syphilis (odd ratio [OR] = 3.1; 95% confidence limits [CL] = 2.0, 4.8), and having had two or more lifetime heterosexual partners (OR = 3.2; 95% CL = 1.6, 6.4). In this community, HBV infection was transmitted predominantly by heterosexual contact.