Ruth Milner

Agreement among reviewers of review articles.

OBJECTIVE To assess the consistency of an index of the scientific quality of research overviews. DESIGN Agreement was measured among nine judges, each of whom assessed the scientific quality of 36 published review articles. ITEM SELECTION: An iterative process was used to select ten criteria relative to five key tasks entailed in conducting a research overview. SAMPLE The review articles were drawn from three sampling frames: articles highly rated by criteria external to the study; meta-analyses; and a broad spectrum of medical journals. JUDGES: Three categories of judges were used: research assistants; clinicians with research training; and experts in research methodology; with three judges in each category. RESULTS The level of agreement within the three groups of judges was similar for their overall assessment of scientific quality and for six of the nine other items. With four exceptions, agreement among judges within each group and across groups, as measured by the intraclass correlation coefficient (ICC), was greater than 0.5, and 60% (24/40) of the ICCs were greater than 0.7. CONCLUSIONS It was possible to achieve reasonable to excellent agreement for all of the items in the index, including the overall assessment of scientific quality. The implications of these results for practising clinicians and the peer review system are discussed.

Decreased disability rate among 3-year-old survivors weighing 501 to 1000 grams at birth and born to residents of a geographically defined region from 1981 to 1984 compared with 1977 to 1980+

In this article we report the survival and morbidity rates for all live-born infants weighing 501 to 1000 gram at birth and born to residents of a defined geographic region from 1977 to 1980 (n = 255) compared with 1981 to 1984 (n = 266). During these periods, there were no changes in the proportion of infants delivered at the tertiary care center or community hospitals (171/84 vs 194/72); use of the tertiary care center increased only slightly, from 84% to 91%; and changes in neonatal management were mainly in improvements in diagnostic and monitoring techniques. When infants were grouped according to birth weights in 100 gm increments, survival improved significantly only for infants weighing between 501 and 600 gm at birth (2% vs 20% p less than 0.001). There were no differences in the overall survival rates to hospital discharge (46% vs 48%). The prevalence of neurosensory impairments was 24% in period 1 and 17% in period 2. There was a significant improvement in the proportion of infants considered to have disabilities by a functional classification assigned at 3 years corrected age (50% vs 27%, p less than 0.001), but only for infants weighing more than 800 gm at birth (49% vs 22%, p less than 0.001). Infants delivered at the community hospitals had a higher prevalence of neurosensory impairments compared with infants delivered at the tertiary care center (period 1, 35% vs 21%, not significant; period 2, 37% vs 14%, p less than 0.05). These data are encouraging; further efforts should be directed toward assessing which, if any, components of perinatal care are contributing to the improvement in morbidity rates.

Follow-up of infants 501 to 1,500 gm birth weight delivered to residents of a geographically defined region with perinatal intensive care facilities

In an attempt to minimize the selection bias inherent in reporting the outcome of premature infants from a particular neonatal intensive care unit, this study presents data on all 294 live births 501 to 1,500 gm birth weight born to residents in the Hamilton-Wentworth region during 1973-78. The survival rate was 31.9% in infants less than or equal to 1,000 gm and 82.6% in infants between 1,001 to 1,500 gm. In all, 184 infants (62.6%) were discharged alive and 37 of these had weight less than or equal to 1,000 gm. The mean BW of the survivors was 1,216 +/- 214 gm and the mean gestation was 30.0 +/- 2.9 weeks, with 18.0% being small-for-gestational age. Neurologic handicaps including cerebral palsy, hydrocephalus, microcephaly, blindness, deafness, and mental retardation occurred in 30/179 (16.8%) survivors. The incidence of neurologic handicaps was 30% among babies who received IPPV versus 10% in those who did not. Within the IPPV and non-IPPV groups, there were no significant differences in handicap rates by 500 gm BW class.

A multicenter study of the treatment of childhood chronic idiopathic thrombocytopenic purpura with anti-D

We evaluated the effects of the intravenous administration of anti-D, an immune globulin directed at the D antigen on erythrocytes that is purified from plasma from sensitized persons, on patients with idiopathic thrombocytopenic purpura. To determine the most effective dose, the duration of response, and the side effects of this therapy in children, we performed a multicenter cohort study of escalating doses of intravenously administered anti-D in children aged 1 to 18 years with chronic idiopathic thrombocytopenic purpura, defined as idiopathic thrombocytopenic purpura persisting for more than 6 months with a platelet count of less than 50 x 10(9) cells/L. Twenty-five Rh-positive children received increasing doses of anti-D as follows: day 1, 25 micrograms/kg; day 2, 25 micrograms/kg; day 7, 35 micrograms/kg; day 14, 45 micrograms/kg; and day 21, 55 micrograms/kg. Administration of anti-D was stopped after day 21 or when the platelet count rose to greater than 150 x 10(9) cells/L or the hemoglobin level was 100 gm/L. Platelet count was less than 50 x 10(9) cells/L in all children before treatment. A response was defined as an increase in the platelet count to more than 50 x 10(9)/L and a doubling of the pretreatment platelet count. Of 25 children, 23 (92%) had responses by day 7 of the initial treatment protocol. Eighteen children (72%) had platelet counts greater than 150 x 10(9) cells/L by day 7 after two doses of anti-D. Median duration of response was 5 weeks (range 1 to 24 weeks). Average drop in hemoglobin level was 13.7 gm/L; in one child (a nonresponder) hemoglobin value fell to less than 100 gm/L. No other untoward side effects were seen. Of the 23 children who responded, 21 were retreated with one dose of anti-D when platelet counts returned to baseline values of less than 50 x 10(9) cells/L; all but three of the children who underwent retreatment showed a response the second time. Sixteen children continued to receive intermittent anti-D therapy after completion of the study, and all continued to have excellent responses. We conclude that anti-D is a safe, effective, and relatively inexpensive therapy for childhood chronic idiopathic thrombocytopenic purpura.

A randomized clinical trial of the Leboyer approach to childbirth.

To examine the effects of the Leboyer method of delivery, we randomly assigned 56 women to either a Leboyer or a conventional delivery and used a variety of clinical and behavioral measures to assess the outcome in mother and child. No differences were noted in maternal or newborn morbidity, in infant behavior in the first hour of life, at 24 or 72 hours post partum, or at eight months of age; or in maternal perceptions of her infant and the experience of giving birth, except that eight months after delivery, mothers who had used the Leboyer method were more likely to say that the event had influenced their childs behavior (P = 0.05). Women who expected a Leboyer delivery had shorter active labors (P = 0.03), suggesting that psychologic factors (expectations) influence physical outcomes in perinatal medicine. Our results suggest that the Leboyer procedure has no advantage over a gentle, conventional delivery in influencing infant and maternal outcomes.

Effect of delivery method on outcomes in the very low-birth weight breech infant: Is the improved survival related to cesarean section or other perinatal care maneuvers?

The perinatal mortality rate among very low-birth weight infants has been decreased by 20% during the last 4 years of the 1973 to 1980 period here reported. The concurrent increase in the cesarean section rate from 11.9% to 49.1% during the same time frames has been assumed to be responsible for the improved outcome. The changes were most marked in the extremely low-birth weight group (less than 1,000 gm). The survival rates and cesarean section rates were examined among infants of similar birth weight and gestational age in the vertex presentation, in the same time frames. A similar or greater reduction in mortality rate (from 85% to 45%) was noted in the very low-birth weight vertex infants, whereas the cesarean section rate remained minimally and not significantly increased (14.2% to 22.2%). The interpretation of this finding is by no means clear but must include the hypothesis that the increased cesarean section rate may be incidental and in no way related to the improved outcome. The most statistically significant determinants of outcome remain birth weight and gestational age strata, with no significant difference in outcomes when the extremely low-birth weight group is analyzed separately from the entire very low-birth weight group. As yet unidentified perinatal care practices, other than cesarean section, may be more likely to affect outcome in this high-risk group.

Erythropoietin therapy in neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions

OBJECTIVES To determine whether treatment with recombinant human erythropoietin (r-HuEPO) reduces transfusion requirements in premature neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions. STUDY DESIGN A double-blind, randomized, controlled trial. SUBJECTS Fifty-five infants appropriate in weight for gestational age (less than 1250 gm birth weight) who, at 10 days of age, were predicted to have a greater than 75% probability of having bronchopulmonary dysplasia. This criterion had previously been shown to identify infants requiring multiple transfusions. Twenty-seven infants were randomly assigned to receive r-HuEPO therapy and 28 to a control group. r-HuEPO was administered in a dosage of 20 U/kg body weight, subcutaneously, three times a week for 6 weeks. Control infants received sham treatment. RESULTS Infants treated with r-HuEPO required significantly fewer transfusions than control infants during their entire hospital stay (mean 3.48 +/- 1.58 vs 5.68 +/- 2.30; p = 0.0001) and had a higher mean reticulocyte count (p < or = 0.0005) and a higher mean hemoglobin concentration (p < or = 0.005) during the treatment period. At follow-up, 4 months after term, there were no significant differences between the groups in mean reticulocyte count (p = 0.86) or mean hemoglobin concentration (p = 0.56). However, two infants in each group had low serum ferritin values indicative of depleted iron stores. CONCLUSIONS Treatment with r-HuEPO effectively stimulated erythropoiesis in premature infants at high risk of having bronchopulmonary dysplasia and requiring multiple transfusions; the result was a reduction in transfusion requirements. This treatment, together with other strategies to reduce the need for transfusions, is appropriate in this population. Unrelated to r-HuEPO treatment, these infants may be at risk of having iron deficiency later in infancy.

Clinical and laboratory diagnosis of hemostatic disorders in newborn infants.

We describe a microtechnology for the study of the coagulation system in newborn infants. Interpretation of results demands an understanding of the techniques used and the nature of the control population from which normal values are drawn. We have examined two syndromes which represent the majority of hemostatic disorders of sick newborn infants. The first is thrombocytopenia resulting from bacterial infections in which there are minimal changes in the levels of blood coagulation factors and little tendency to bleed. The second is a syndrome of disseminated intravascular coagulation in which there is a profound disturbance in the coagulation mechanism, relatively little change in platelet counts, a severe hemorrhagic diathesis, and widespread ischemic necrosis.

A PHASE II RANDOMIZED CONTROLLED TRIAL OF SYNSORB-PK FOR THE PREVENTION OF HEMOLYTIC UREMIC SYNDROME IN CHILDREN WITH VEROTOXIN-PRODUCING E. COLI (VTEC) GASTROENTERITIS. † 1684

A PHASE II RANDOMIZED CONTROLLED TRIAL OF SYNSORB-PK FOR THE PREVENTION OF HEMOLYTIC UREMIC SYNDROME IN CHILDREN WITH VEROTOXIN-PRODUCING E. COLI (VTEC) GASTROENTERITIS. † 1684

Factors XI and XII are low in subjects with liver disease

We prospectively measured levels of factors XI and XII in parallel with other coagulation factors in 39 unselected patients with liver disease and in 20 control subjects. Mean levels of factors XI and XII in subjects with liver disease were significantly reduced, being 58% and 61%, respectively, compared with 100% and 94% in controls. Reductions in levels of factors XI and XII were most pronounced in those subjects with low serum albumin. The partial thromboplastin time (APTT) reflected low levels of either factor XI or XII and was most prolonged when both were low, but cause and effect was not demonstrated. Low levels of these factors may explain previous reports of poor response of APTT to infusions of prothrombin complex concentrates. Finally, these low levels strongly suggest that factors XI and XII are produced in the liver.We prospectively measured levels of factors XI and XII in parallel with other coagulation factors in 39 unselected patients with liver disease and in 20 control subjects. Mean levels of factors XI and XII in subjects with liver disease were significantly reduced, being 58% and 61%, respectively, compared with 100% and 94% in controls. Reductions in levels of factors XI and XII were most pronounced in those subjects with low serum albumin. The partial thromboplastin time (APTT) reflected low levels of either factor XI or XII and was most prolonged when both were low, but cause and effect was not demonstrated. Low levels of these factors may explain previous reports of poor response of APTT to infusions of prothrombin complex concentrates. Finally, these low levels strongly suggest that factors XI and XII are produced in the liver.