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Screening for pediatric lead poisoning: Comparability of simultaneously drawn capillary and venous blood samples
CURRENT LITERATURE AND CLINICAL ISSUES
Abstracts from the literature Protection against hepatitis A by an inactivated vaccine Innis BL, Snitbhan R, Kunasol P, et al. J A M A 1994; 271:1328-34.
Objective: To evaluate the safety and efficacy of a new inactivated hepatitis A vaccine. Design: Double-blind, randomized, controlled trial stratified by community. Setting: Community based in Thailand. Study participants: A total of 40,119 children, aged 1 to 16 years,.attending 148 primary schools: 38,157 (95%) entered surveillance a mean of 138 days after receiving vaccine dose 1; 33,586 (84%) completed the controlled trial of 532 days; and 31,075 (81%) received crossover vaccine and remained under surveillance until day 844. Intervention: Participants received hepatitis A vaccine or control hepatitis B vaccine starting Jan. 7, 1991 (doses at baseline and in months 1 and 12), and crossed over to the alternative vaccine 18 months later. Main outcome measure: Cases of hepatitis A (symptoms, alanine aminotransferase levels of 45 U / L or higher, and IgM to hepatitis A virus) were identified by evaluating school absences of 2 or more days. Results: There were no serious adverse reactions despite administration of more than 109,000 doses of hepatitis A vaccine. Among initially seronegative recipients of two doses of hepatitis A vaccine, the proportion with 20 m l U / m l or more of antibody to hepatitis A virus before and 5 months after a 1-year booster was 94% and 99%, respectively. Of 6976 episodes of illness during the controlled trial, there were 40 cases of hepatitis A; 38 were in the control group. Of the 40 cases, six, all in control subjects, occurred after the 1-year booster dose. After two doses of hepatitis A vaccine (days 138 through 386), protective efficacy was 94% (95% confidence interval, 79% to 99%); cumulative efficacy, including the postbooster period (days 138 to 532), was 95% (95% confidence interval, 82% to 99%). The two hepatitis A vaccine recipients with symptomatic infections (257 and 267 days after dose 1) may have been partially protected; their illnesses were brief and associated with only slight increases in alanine aminotransferase activity. Conclusions." Inactivated hepatitis A vaccine is safe; when administered in two doses, it protects against hepatitis A for at least 1 year. Comment: This remarkable clinical trial of a new hepatitis A vaccine performed among 40,119 children in Thailand is The Journal of Pediatrics
the second clinical trial to document the efficacy of formalin-inactivated hepatitis A vaccine. A similar vaccine was tested among children in Monroe, N.Y., and the results were reported in 1992.1 Both vaccines demonstrated a high level of clinical efficacy in the prevention of symptomatic hepatitis, but both trials suffer somewhat from reliance on IgM antibodies as a marker of disease. This may be cause problems after immunization because prior exposure to antigen may blunt the IgM response should a vaccinee become infected. Comparison of vaccine studies is also hampered by the lack of standardized methods for quantitation of antibody response to vaccine. It seems likely, however, that these vaccines are similar in efficacy and would be effective in adults. The economic burden of hepatitis A in the United States exceeds $200 million annually, and the changing epidemiology of the disease is leading to more infections among older people, in whom severe hepatitis is more likely to develop. Compared with the short-term protection afforded by immune globulin, inactivated hepatitis A vaccine will likely induce protection lasting for 5 to 10 years or even longer. Who, then, should receive this vaccine? Targeting high-risk groups is no more likely to be effective for hepatitis A than it was for hepatitis B; universal childhood immunization is a possibility but is not likely to be recommended in the near future. Rigorous cost-benefit analyses will be needed to determine how the vaccines might best be used, but inactivated hepatitis A vaccines will probably come to play an important role in the control of viral hepatitis.
Stanley M. Lemon, MD Department of Medicine University of North Carolina at Chapel Hill Chapel Hill NC 27599-7030 REFERENCES
1. Werzberger A, Mensch B, Kuter B, et al. A controlled trial of a formalin-inactivated hepatitis A vaccine in healthy children. N Engl J Med 1992;327:453-7.
Screening for pediatric lead poisoning: Comparability of simultaneously drawn capillary and venous blood samples Schlenker TL, Fritz CJ, Mark D, et al. J A M A 1994; 271:1346-8.
Objective: To determine the ability of capillary blood lead levels to reflect true blood lead levels accurately in children at risk of acquiring lead poisoning. Design." A correlation study in which lead levels in capillary November 1994
839
840
Abstracts from the literature
blood specimens obtained by four different methods were compared with lead levels in simultaneously drawn venous blood specimens. Setting." A central-city pediatric primary care clinic and door-to-door home visits in one central-city neighborhood. Patients: Two hundred ninety-five children aged 6 months to 6 years, at high risk of acquiring lead poisoning. Main outcome measures: Blood lead levels of simultaneously drawn capillary and venous blood specimens. Results: Lead levels of all four capillary sampling methods were highly correlated (correlation coefficient >__0.96) with matched venous blood lead levels, with mean capillary-venous differences less than 0.05 /~mol/L (1 #g/ dl). Conclusions: Capillary sampling is an acceptable alternative to venipuncture for lead-poisoning screening in young children. Comment: In 1991 the Centers for Disease Control and Prevention recommended universal screening for childhood lead poisoning. 1 However, the ages when children are at highest risk are also the ages when venipunctures are the most difficult, so a practical alternative would be welcome. This study is one of the first to address the reliability of capillary blood lead levels in comparison with simultaneously drawn venous samples. One concern with this study is that two different laboratory techniques were used: flame atomic-absorption spectrophotometry with Delves-cup modification, and graphite furnace atomic-absorption spectrophotometry. This is a possible source of measurement bias if the two methods differ in terms of accuracy or precision. However, previous studies have shown that the differences may be clinically insignificant.2 Nevertheless, a statement regarding how many tests were conducted by each method and which samples were measured by which technique would be helpful. The population studied was presumed to be at high risk because of inner-citY residence, but no objective measure of risk status was reported. The comparison of capillary with venous lead levels was made for a wide range of Values, making this study generalizable to most screening situations. This article demonstrates that capillary testing can work (efficacy). The questions of whether it does work in the routine situation (effectiveness) and the more important question of whether it is worth doing (efficiency) will need to be answered by larger field studies. Lynnette J. Mazur, MD, M P H Department o f Pediatrics University o f Texas Medical School at Houston Houston, T X 77030
The Journal of Pediatrics November 1994
REFERENCES
1. Centers for Disease Control. Preventing lead poisoning in young children. U.S. Department of Health and Human Services Report 537-304, 1991. 2. Miller DT, Paschal DC, Gunter PE, et al. Determination of lead in blood using electrothermal atomization atomic absorption speetrophotometry with a L'vov platform and matrix modifier. Analyst 1987;112:1701-5.
A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-lowbirth-weight infants Fanaroff AA, Korones SB, Wright LL, eL al. N Engl J Med 1994;330:1107-13. Objective: To determine whether prophylactic intravenous administration of immune globulin (IVIG) reduces the rate of hospital-acquired infections in premature infants. Design: Prospective, multicenter, two-phase controlled trial. Phase 1 had a double-blind design; phase 2 did not. Setting." Ten neonatal centers in the United States. Patients: A total of 2416 infants stratified according to birth weight (501 to 1000 gm and 1001 to 1500 gin). Intervention: Infants were randomly assigned to an IVIG group (n = 1204) or a control group (n = 1212). Control infants were given placebo infusions during phase 1 of the study (n = 623) but were not given any infusions during phase 2 (n = 589). Infants who weighed 501 to 1000 gm at birth were given 900 mg of IVIG per kilogram of body weight, and infants weighing 1001 to 1500 gm at birth were given a dose of 700 mg/kg. The IVIG infusions were repeated every 14 days until the infants weighed 1800 gin, were transferred to another center, died, or were sent home from the hospital. Results: Nosocomial infections of the blood, meninges, or urinary tract occurred in 439 of the 2416 infants (18.2%): 208 (17.3%) in the IVIG group and 231 (19.1%) in the control group (relative risk, 0.91; 95% confidence interval, 0.77 to 1.08). Septicemia occurred in 15.5% of the IVIG recipients and 17.2% of the control subjects. During phase 1, the rate of nosocomial infections was 13.4% in the IVIG group and 17.8% in the control group; the respective rates during phase 2 were 21.0% and 20.4%. The predominant Organisms included gram-positive cocci (53.0%), gramnegative bacilli (22.4%), and Candida species (16.0%). Adverse reactions were rarely observed during the infusions. Therapy with IVIG had no effect on the incidence of respiratory distress syndrome, bronchopulmonary dysplasia, or intracranial hemorrhage, on the duration of hospitalization, or on the mortality rate. The incidence of necrotizing enterocolitis (NEC) was 12.0% in the IVIG group and 9.5% in the control group.
Abstracts from the literature Protection against hepatitis A by an inactivated vaccine Innis BL, Snitbhan R, Kunasol P, et al. J A M A 1994; 271:1328-34.
Objective: To evaluate the safety and efficacy of a new inactivated hepatitis A vaccine. Design: Double-blind, randomized, controlled trial stratified by community. Setting: Community based in Thailand. Study participants: A total of 40,119 children, aged 1 to 16 years,.attending 148 primary schools: 38,157 (95%) entered surveillance a mean of 138 days after receiving vaccine dose 1; 33,586 (84%) completed the controlled trial of 532 days; and 31,075 (81%) received crossover vaccine and remained under surveillance until day 844. Intervention: Participants received hepatitis A vaccine or control hepatitis B vaccine starting Jan. 7, 1991 (doses at baseline and in months 1 and 12), and crossed over to the alternative vaccine 18 months later. Main outcome measure: Cases of hepatitis A (symptoms, alanine aminotransferase levels of 45 U / L or higher, and IgM to hepatitis A virus) were identified by evaluating school absences of 2 or more days. Results: There were no serious adverse reactions despite administration of more than 109,000 doses of hepatitis A vaccine. Among initially seronegative recipients of two doses of hepatitis A vaccine, the proportion with 20 m l U / m l or more of antibody to hepatitis A virus before and 5 months after a 1-year booster was 94% and 99%, respectively. Of 6976 episodes of illness during the controlled trial, there were 40 cases of hepatitis A; 38 were in the control group. Of the 40 cases, six, all in control subjects, occurred after the 1-year booster dose. After two doses of hepatitis A vaccine (days 138 through 386), protective efficacy was 94% (95% confidence interval, 79% to 99%); cumulative efficacy, including the postbooster period (days 138 to 532), was 95% (95% confidence interval, 82% to 99%). The two hepatitis A vaccine recipients with symptomatic infections (257 and 267 days after dose 1) may have been partially protected; their illnesses were brief and associated with only slight increases in alanine aminotransferase activity. Conclusions." Inactivated hepatitis A vaccine is safe; when administered in two doses, it protects against hepatitis A for at least 1 year. Comment: This remarkable clinical trial of a new hepatitis A vaccine performed among 40,119 children in Thailand is The Journal of Pediatrics
the second clinical trial to document the efficacy of formalin-inactivated hepatitis A vaccine. A similar vaccine was tested among children in Monroe, N.Y., and the results were reported in 1992.1 Both vaccines demonstrated a high level of clinical efficacy in the prevention of symptomatic hepatitis, but both trials suffer somewhat from reliance on IgM antibodies as a marker of disease. This may be cause problems after immunization because prior exposure to antigen may blunt the IgM response should a vaccinee become infected. Comparison of vaccine studies is also hampered by the lack of standardized methods for quantitation of antibody response to vaccine. It seems likely, however, that these vaccines are similar in efficacy and would be effective in adults. The economic burden of hepatitis A in the United States exceeds $200 million annually, and the changing epidemiology of the disease is leading to more infections among older people, in whom severe hepatitis is more likely to develop. Compared with the short-term protection afforded by immune globulin, inactivated hepatitis A vaccine will likely induce protection lasting for 5 to 10 years or even longer. Who, then, should receive this vaccine? Targeting high-risk groups is no more likely to be effective for hepatitis A than it was for hepatitis B; universal childhood immunization is a possibility but is not likely to be recommended in the near future. Rigorous cost-benefit analyses will be needed to determine how the vaccines might best be used, but inactivated hepatitis A vaccines will probably come to play an important role in the control of viral hepatitis.
Stanley M. Lemon, MD Department of Medicine University of North Carolina at Chapel Hill Chapel Hill NC 27599-7030 REFERENCES
1. Werzberger A, Mensch B, Kuter B, et al. A controlled trial of a formalin-inactivated hepatitis A vaccine in healthy children. N Engl J Med 1992;327:453-7.
Screening for pediatric lead poisoning: Comparability of simultaneously drawn capillary and venous blood samples Schlenker TL, Fritz CJ, Mark D, et al. J A M A 1994; 271:1346-8.
Objective: To determine the ability of capillary blood lead levels to reflect true blood lead levels accurately in children at risk of acquiring lead poisoning. Design." A correlation study in which lead levels in capillary November 1994
839
840
Abstracts from the literature
blood specimens obtained by four different methods were compared with lead levels in simultaneously drawn venous blood specimens. Setting." A central-city pediatric primary care clinic and door-to-door home visits in one central-city neighborhood. Patients: Two hundred ninety-five children aged 6 months to 6 years, at high risk of acquiring lead poisoning. Main outcome measures: Blood lead levels of simultaneously drawn capillary and venous blood specimens. Results: Lead levels of all four capillary sampling methods were highly correlated (correlation coefficient >__0.96) with matched venous blood lead levels, with mean capillary-venous differences less than 0.05 /~mol/L (1 #g/ dl). Conclusions: Capillary sampling is an acceptable alternative to venipuncture for lead-poisoning screening in young children. Comment: In 1991 the Centers for Disease Control and Prevention recommended universal screening for childhood lead poisoning. 1 However, the ages when children are at highest risk are also the ages when venipunctures are the most difficult, so a practical alternative would be welcome. This study is one of the first to address the reliability of capillary blood lead levels in comparison with simultaneously drawn venous samples. One concern with this study is that two different laboratory techniques were used: flame atomic-absorption spectrophotometry with Delves-cup modification, and graphite furnace atomic-absorption spectrophotometry. This is a possible source of measurement bias if the two methods differ in terms of accuracy or precision. However, previous studies have shown that the differences may be clinically insignificant.2 Nevertheless, a statement regarding how many tests were conducted by each method and which samples were measured by which technique would be helpful. The population studied was presumed to be at high risk because of inner-citY residence, but no objective measure of risk status was reported. The comparison of capillary with venous lead levels was made for a wide range of Values, making this study generalizable to most screening situations. This article demonstrates that capillary testing can work (efficacy). The questions of whether it does work in the routine situation (effectiveness) and the more important question of whether it is worth doing (efficiency) will need to be answered by larger field studies. Lynnette J. Mazur, MD, M P H Department o f Pediatrics University o f Texas Medical School at Houston Houston, T X 77030
The Journal of Pediatrics November 1994
REFERENCES
1. Centers for Disease Control. Preventing lead poisoning in young children. U.S. Department of Health and Human Services Report 537-304, 1991. 2. Miller DT, Paschal DC, Gunter PE, et al. Determination of lead in blood using electrothermal atomization atomic absorption speetrophotometry with a L'vov platform and matrix modifier. Analyst 1987;112:1701-5.
A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-lowbirth-weight infants Fanaroff AA, Korones SB, Wright LL, eL al. N Engl J Med 1994;330:1107-13. Objective: To determine whether prophylactic intravenous administration of immune globulin (IVIG) reduces the rate of hospital-acquired infections in premature infants. Design: Prospective, multicenter, two-phase controlled trial. Phase 1 had a double-blind design; phase 2 did not. Setting." Ten neonatal centers in the United States. Patients: A total of 2416 infants stratified according to birth weight (501 to 1000 gm and 1001 to 1500 gin). Intervention: Infants were randomly assigned to an IVIG group (n = 1204) or a control group (n = 1212). Control infants were given placebo infusions during phase 1 of the study (n = 623) but were not given any infusions during phase 2 (n = 589). Infants who weighed 501 to 1000 gm at birth were given 900 mg of IVIG per kilogram of body weight, and infants weighing 1001 to 1500 gm at birth were given a dose of 700 mg/kg. The IVIG infusions were repeated every 14 days until the infants weighed 1800 gin, were transferred to another center, died, or were sent home from the hospital. Results: Nosocomial infections of the blood, meninges, or urinary tract occurred in 439 of the 2416 infants (18.2%): 208 (17.3%) in the IVIG group and 231 (19.1%) in the control group (relative risk, 0.91; 95% confidence interval, 0.77 to 1.08). Septicemia occurred in 15.5% of the IVIG recipients and 17.2% of the control subjects. During phase 1, the rate of nosocomial infections was 13.4% in the IVIG group and 17.8% in the control group; the respective rates during phase 2 were 21.0% and 20.4%. The predominant Organisms included gram-positive cocci (53.0%), gramnegative bacilli (22.4%), and Candida species (16.0%). Adverse reactions were rarely observed during the infusions. Therapy with IVIG had no effect on the incidence of respiratory distress syndrome, bronchopulmonary dysplasia, or intracranial hemorrhage, on the duration of hospitalization, or on the mortality rate. The incidence of necrotizing enterocolitis (NEC) was 12.0% in the IVIG group and 9.5% in the control group.