Combination chemotherapy in refractory immune thrombocytopenic purpura

BACKGROUND: Chronic idiopathic thrombocytopenic purpura is a destructive thrombocytopenia caused by an autoantibody. About 80 percent of patients with chronic idiopathic thrombocytopenic purpura have remissions after either corticosteroid therapy or splenectomy. Some patients with resistant disease respond to other agents, but a substantial group are refractory to therapy. METHODS: We used combination chemotherapy to treat 10 patients with refractory immune thrombocytopenia. An average of 6.8 (range, 3 to 10) previous therapies, including corticosteroids and splenectomy, had been unsuccessful in these patients. The patients received from three to eight cycles of therapy consisting of cyclophosphamide and prednisone combined with either vincristine (one patient), vincristine and procarbazine (four patients), or etoposide (six patients, including one patient who received four cycles each containing procarbazine and etoposide). RESULTS: Among the 10 patients, 6 had complete responses (platelet count, > 180,000 per cubic millimeter); of these, 4 patients had responses that persisted for more than 11, 30, 54, or 126 months, 1 had a relapse 9 months after therapy but had a remission with further therapy and remained in remission for 48 months before dying of an unrelated illness, and another relapsed just before her fifth course of therapy. Two patients had partial responses (platelet count, > 50,000 per cubic millimeter); the platelet counts in one remained stable for more than nine months after the end of therapy, and the other patient relapsed. The remaining two patients had no response. Complete responses were associated with a disappearance or marked decrease in the level of platelet-associated autoantibody. CONCLUSIONS: Combination chemotherapy is beneficial in some patients in whom immune thrombocytopenia is refractory to corticosteroids and splenectomy.     

Outpatient management without antibiotics of fever in selected infants

BACKGROUND: In many academic centers it is standard practice to hospitalize all febrile infants younger than two months of age, whereas in community settings such infants are often cared for as outpatients. METHODS: We conducted a controlled study of 747 consecutive infants 29 through 56 days of age who had temperatures of at least 38.2 degrees C. After a complete history taking, physical examination, and sepsis workup, the 460 infants with laboratory or clinical findings suggestive of serious bacterial illness were hospitalized and treated with antibiotics. The screening criteria for serious bacterial illness included a white-cell count of at least 15,000 per cubic millimeter, a spun urine specimen that had 10 or more white cells per high-power field or that was positive on bright-field microscopy, cerebrospinal fluid with a white-cell count of 8 or more per cubic millimeter or a positive Gram's stain, or a chest film showing an infiltrate. The 287 infants who had unremarkable examinations and normal laboratory results were assigned to either inpatient observation without antibiotics (n = 148) or outpatient care without antibiotics but with reexaminations after 24 and 48 hours (n = 139). RESULTS: Serious bacterial illness was diagnosed in 65 infants (8.7 percent). Of these 65 infants, 64 were identified by our screening criteria for inpatient care and antibiotic treatment (sensitivity = 98 percent; 95 percent confidence interval, 92 to 100). Of the 287 infants assigned to observation and no antibiotics, 286 (99.7 percent) did not have serious bacterial illness. Only two infants assigned to outpatient observation were subsequently admitted to the hospital; neither was found to have a serious illness. Outpatient care without antibiotics of the febrile infants at low risk for serious illness resulted in a savings of about $3,100 per patient. CONCLUSIONS: With the use of strict screening criteria, a substantial number of febrile one-to-two-month-old infants can be cared for safely as outpatients and without antibiotics.     

Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage

OBJECTIVE: The antenatal and intrapartum management of women with autoimmune thrombocytopenia is controversial. The current approach emphasizes an effort to identify maternal characteristics predictive of severe neonatal thrombocytopenia or to measure fetal platelet counts and perform cesarean section in patients considered to be at risk for neonatal intracranial hemorrhage. In the current study we review our experience with maternal autoimmune thrombocytopenia and neonatal outcome. STUDY DESIGN: Fifty-five pregnancies with autoimmune thrombocytopenia over a 10-year period in three major medical centers in San Diego, California, were evaluated. Maternal characteristics and neonatal outcomes were assessed and compared with those in other recent reports. Data were submitted to Fisher's exact (two-tailed), chi2, and Student t tests, with linear regression performed to analyze the association between variables. RESULTS: Maternal characteristics including platelet count, presence of antiplatelet antibody, antecedent history of autoimmune thrombocytopenia, and corticosteroid therapy were not predictive of severe neonatal thrombocytopenia. Maternal history of splenectomy was significantly correlated with fetal platelet counts <50 x 10(9)/L (odds ratio 5.63; 95% confidence interval 2.2 to 14.3). There were four neonates with severe neonatal thrombocytopenia (8%), and one who was delivered by cesarean section had intracranial hemorrhage. CONCLUSIONS: These findings, combined with others in the literature, confirm that severe neonatal thrombocytopenia is an infrequent complication of maternal autoimmune thrombocytopenia and is not reliably predicted by maternal characteristics. Intracranial hemorrhage is also a rare event and is not related to mode of delivery. Cesarean section should be reserved for obstetric indications only.     

The care of HIV-infected adults in the United States. HIV Cost and Services Utilization Study Consortium

BACKGROUND AND METHODS: In order to elucidate the medical care of patients with human immunodeficiency virus (HIV) infection in the United States, we randomly sampled HIV-infected adults receiving medical care in the contiguous United States at a facility other than military, prison, or emergency department facility during the first two months of 1996. We interviewed 76 percent of 4042 patients selected from among the patients receiving care from 145 providers in 28 metropolitan areas and 51 providers in 25 rural areas. RESULTS: During the first two months of 1996, an estimated 231,400 HIV-infected adults (95 percent confidence interval, 162,800 to 300,000) received care. Fifty-nine percent had the acquired immunodeficiency syndrome according to the case definition of the Centers for Disease Control and Prevention, and 91 percent had CD4+ cell counts of less than 500 per cubic millimeter. Eleven percent were 50 years of age or older, 23 percent were women, 33 percent were black, and 49 percent were men who had had sex with men. Forty-six percent had incomes of less than $10,000 per year, 68 percent had public health insurance or no insurance, and 30 percent received care at teaching institutions. The estimated annual direct expenditures for the care of the patients seen during the first two months of 1996 were $5.1 billion; the expenditures for the estimated 335,000 HIV-infected adults seen at least as often as every six months were $6.7 billion, which is about $20,000 per patient per year. CONCLUSIONS: In this national survey we found that most HIV-infected adults who were receiving medical care had advanced disease. The patient population was disproportionately male, black, and poor. Many Americans with diagnosed or undiagnosed HIV infection are not receiving medical care at least as often as every six months. The total cost of medical care for HIV-infected Americans accounts for less than 1 percent of all direct personal health expenditures in the United States.     

Abciximab-induced thrombopenia during treatment of acute coronary syndromes by angioplasty

ReoPro (abciximab) is the Fab fragment of a chimeric monoclonal antibody directed against platelet glycoprotein IIb-IIIa. Its efficacy to prevent ischaemic complications after PTCA has been demonstrated in 3 studies: EPIC, EPILOG, UPTAKE. One hundred and sixty five cases of thrombocytopenia (< 100,000/microliter) were reported in a series of 5461 patients randomized in these 3 studies (i.e. 3.0%), including 46 (2.03%) with placebo and 119 (3.73% with abciximab. Among the 2270 patients randomized to receive placebo, 11 (0.48%) cases of severe thrombocytopenia (< 50,000/microliter) were observed versus 34 (1.07%) with abciximab. Major acute thrombocytopenia (< 20,000/microliter and < 24 hours) occurred in 0.60% (20 patients) of cases with abciximab. Their mechanism remains unknown. A therapeutic challenge did not modify either their incidence, or their severity. The development of thrombocytopenia did not worsen the patient's prognosis and course was always favourable. Twenty five cases of thrombocytopenia (0.60%), including 3 cases of acute major thrombocytopenia (0.08%) were spontaneously reported in France among the first 4000 patients treated with abciximab post-marketing. All patients treated with abciximab must be monitored by platelet count, 2 to 4 hours after the bolus administration, then 12 and 24 hours later. These platelet counts should be performed on 3 tubes (EDTA, citrate, heparin) in order to eliminate pseudothrombocytopenia and a differential diagnosis. In the case of true thrombocytopenia (< 10,000/l), treatment should be suspended and the platelet count should be repeated daily until return to normal. In the case of thrombocytopenia less than 60,000/microliter, heparin and aspirin should also be systematically discontinued and, below 50,000/microliter, platelet transfusion is justified.     

Diltiazem-associated thrombocytopenia

Nine days after starting diltiazem therapy for new-onset atrial fibrillation, a patient's platelet count had diminished to 61 x 10(3)/mm3, and 2 weeks later the nadir was reached at 23 x 10(3)/mm3. No hypersensitivity reaction otherwise was noted, and other hematologic values were unaffected. The patient's platelet counts were not affected by platelet transfusions. Bone marrow examination showed normal to increased numbers of megakaryocytes, suggesting peripheral destruction. After discontinuing diltiazem and administering high-dose immunoglobulin infusions, the platelet count returned to normal. This case suggests an immune-mediated cause for thrombocytopenia after exposure to diltiazem.     

A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team

BACKGROUND: The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1) infection are not clear. We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine. METHODS: A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count (50 or fewer vs. 51 to 200 cells per cubic millimeter) and randomly assigned to one of two daily regimens: 600 mg of zidovudine (or stavudine) and 300 mg of lamivudine, or that regimen with 2400 mg of indinavir. The primary end point was the time to the development of the acquired immunodeficiency syndrome (AIDS) or death. RESULTS: The proportion of patients whose disease progressed to AIDS or death was lower with indinavir, zidovudine, and lamivudine (6 percent) than with zidovudine and lamivudine alone (11 percent; estimated hazard ratio, 0.50; 95 percent confidence interval, 0.33 to 0.76; P=0.001). Mortality in the two groups was 1.4 percent and 3.1 percent, respectively (estimated hazard ratio, 0.43; 95 percent confidence interval, 0.19 to 0.99; P=0.04). The effects of treatment were similar in both CD4 cell strata. The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results. CONCLUSIONS: Treatment with indinavir, zidovudine, and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine.     

Pregnancy-associated thrombocytopenia revisited: assessment and follow-up of 50 cases

Thrombocytopenia detected during pregnancy addresses the issue of its mechanism and of the possible occurrence of neonatal thrombocytopenia. To further investigate these issues, 50 women referred to us because of thrombocytopenia detected during pregnancy (platelet count, <150 x 10(9)/L), were extensively studied, as well as their offspring. Among these thrombocytopenic women, we used the threshold of 70 x 10(9)/L to differentiate between mild and severe thrombocytopenia. Whatever the severity of thrombocytopenia, we found biological features of an autoimmune disorder in 48% of the women, and chronic thrombocytopenia in 55%. A familial thrombocytopenia was evidenced in 1 case. These 50 women gave birth to 63 neonates, among whom 24 were thrombocytopenic, either at birth or during the first week of life. Neonatal thrombocytopenia could only be predicted in multiparous women, on the basis of previous neonatal thrombocytopenia in older siblings, and/or when maternal platelet life span study, performed before pregnancy, had evidenced an autoimmune thrombocytopenia (AITP)-like profile. These results suggest that, in case of pregnancy-associated thrombocytopenia, familial and immunological studies, combined with postdelivery iterative platelet counts, should be performed to properly characterize the thrombocytopenia. Moreover, the platelet count of the neonate should be carefully assessed at birth and during the following days, a platelet life span study should be performed after delivery in the mother, because these two parameters are likely to bring valuable information regarding the forthcoming pregnancies and the risk of neonatal thrombocytopenia.     

Low fetal morbidity in pregnancy associated with acute and chronic idiopathic thrombocytopenic purpura

Forty-six mothers with immune thrombocytopenic purpura (ITP) gave birth to 72 babies. Sixty-two babies were delivered vaginally and 10 babies by cesarean section. There was no mortality among mothers or babies. Eighteen infants were born thrombocytopenic (PLT < 100 x 10(9)/l). Eleven infants had a platelet count of less than 50 x 10(9)/l. All the severely thrombocytopenic babies (except 1) were born to post splenectomy thrombocytopenic mothers, regardless of steroid treatment during pregnancy. Five babies had clinical manifestations of bleeding; 3 had mild purpura, 1 severe gastrointestinal bleeding, and 1 intracranial bleeding. The latter 2 babies were born prematurely to the same mother who was severely thrombocytopenic despite splenectomy in childhood. In view of very low morbidity in babies of ITP mothers, we suggest that they be delivered vaginally. Cesarean delivery should be performed in selected cases where the mother is severely thrombocytopenic despite splenectomy or where prematurity or obstetrical complications are encountered.     

Maternal flu, fever, and the risk of neural tube defects: a population-based case-control study

Results of clinical and epidemiologic studies have shown an increased risk for neural tube defects (NTD) in infants whose mothers were exposed to heat during pregnancy. However, the risk for NTD in infants whose mothers had influenza during pregnancy has not been well studied. This population-based case-control study of infants born in metropolitan Atlanta, Georgia, from 1968 through 1980 included 385 infants with NTD, 3,647 infants with other birth defects, and 2,676 infants without birth defects. Of the 385 mothers of case infants, 31 reported having a 2-day or longer episode of flu with fever from 1 month before through 3 months after conception (odds ratio (OR) = 3.0; 95% confidence interval (CI) 1.9-4.7). Infants of mothers who took medications for their episodes of flu with fever had an even higher risk for NTD (OR = 4.3, 95% CI 2.6-7.1). When mothers of infants with birth defects other than NTD were used as controls, an increased risk of NTD remained for flu with fever (OR = 1.7, 95% CI 1.1-2.5). There was no increased risk for NTD among the infants of mothers who reported fever from causes other than flu. Because of the heterogeneity of maternal flu, the individual contributions of infection, fever, and medications remain difficult to disentangle.     

Fetal-neonatal thrombocytopenia of immunologic origin: current aspects

Fetal/neonatal immune thrombocytopenias result from increased platelet destruction by maternal antiplatelet antibodies. There is a risk of intracerebral haemorrhage and therefore of neurological impairment or death during the thrombocytopenic period, especially if a defective platelet function co-exists. As no maternal parameter is predictive of the fetal platelet count, the only reliable assessment of the fetal status depends on the fetal blood sampling. Only in case of materno-fetal alloimmunisation the therapy initiated to reverse fetal thrombocytopenia was shown to be effective, but the optimal mode of antenatal treatment is currently under study. As the neonatal therapy and the management of subsequent pregnancies are somehow different it is mandatory to make the distinction between the auto or allo-origin of the fetal thrombocytopenia. The definition of high risk pregnancies will be of help for the development of a routine screening program.     

Sensitivity of resonance thrombograms in thrombocytopenia of dogs

Based on results of 84 blood samples, taken from 28 dogs suffering from thrombocytopenia, the resonance thrombography turned out as a method with low sensitivity (S) to detect thrombocytopenia in dogs. It was insignificant which one of the two tested resonance thrombographs was taken for measurement and which parameter of the resonance thrombogram (RTG) was used for the thrombocytic potential of haemostasis, the amplitude (RTG-P) or descending time of the platelet side. Only samples containing < or = 25,000 platelets/microliter were reliably measured (S > or = 0.90), whereas thrombocytopenias with > 50,000 platelets/microliter usually resulted in false negative results. The correlation between the platelet count and RTG-P could be almost expressed by a geometrical regression (rs = -0.709). The low sensitivity of RTG mirrors the multifactorial influences and contrasts to the exclusive use of RTG in the screening of thrombocytopenia.     

Caring for Cambodian refugees in the emergency department

BACKGROUND: Platelet utilization has steadily increased throughout the past three decades. At the same time, there has been very little study of the current transfusion practices. STUDY DESIGN AND METHODS: A survey was conducted of institutional members of the American Association of Blood Banks (hospitals) that were actively involved in the care of pediatric and/or adult hematology and/or oncology patients. Inquiries were made relating to the extent of prophylactic versus therapeutic use of platelets, criteria used for prophylactic transfusion of platelets and type, and dose of platelets used. Data were analyzed according to patient age and type of hospital. RESULTS: Of 786 responding hospitals, 630 (80.2%) provided sufficient data for analysis; 126 of that 630 provided care for pediatric patients. The majority (60.9%) of responding hospitals had a minimum of four hematologists and/or oncologists. Eighty-four percent of hospitals reported transfusing some apheresis platelets. The dose of platelet concentrates most frequently used for adults ranged from 6 to 10, with pools of 10 more commonly used in community hospitals. More than 70 percent of hospitals reported transfusing platelets primarily for prophylaxis: 60 percent of hospitals set the threshold platelet count for prophylactic platelet transfusion at 20,000 per microL, with approximately 20 percent each transfusing at higher and lower levels. A platelet count of 50,000 per microL was most frequently required for performance of a minor invasive procedure. CONCLUSION: The data from this study show that the majority of institutions use prophylactic platelet transfusion in both pediatric and adult hematology and/or oncology patients. However, there is considerable variation in platelet transfusion practice.     

Relation of parental birth weights to infant birth weight among African Americans and whites in Illinois: a transgenerational study

The authors used a transgenerational data set of Illinois vital records to ascertain the relation between parental birth weights and infant birth weight. The infant generation consisted of all African Americans and whites born in Illinois during 1989-1991. The parent generation included the mothers and fathers who were also born in Illinois between 1956 and 1975. In the infant cohort, the rate of low birth weight (LBW) (<2,500 g) was 11.7% for African Americans (n = 15,287) versus 5.0% for whites (n = 117,708) (relative risk (RR) = 2.3, 95% confidence interval (CI) 2.2-2.5). For African Americans, the LBW rate was 17.9% among those born to LBW mothers (n = 1,943) compared with 10.8% among those born to non-LBW mothers (n = 13,344) (RR = 1.8, 95% CI 1.6-1.9). For whites, the LBW rate was 8.5% among those born to LBW mothers (n = 2,174) compared with 4.8% among those born to non-LBW mothers (n = 115,534) (RR = 1.7, 95% CI 1.6-2.0). A weaker association was observed between paternal birth weight and infant birth weight. The authors conclude that parental birth weights are important risk factors for LBW in both African Americans and whites.     

Urticaria and angioedema: pathophysiology, diagnosis, and treatment

BACKGROUND: Recent case reports suggest that a combination of the appetite suppressants fenfluramine and phentermine is associated with an increased risk of cardiac-valve regurgitation. There are also reports of valvular disorders in persons taking fenfluramine or dexfenfluramine alone, particularly for more than three months. METHODS: We conducted a population-based follow-up study and a nested case-control analysis of 6532 subjects who received dexfenfluramine, 2371 who received fenfluramine, and 862 who received phentermine to assess the risk of a subsequent clinical diagnosis of a valvular disorder of uncertain origin. For comparison, we identified a group of 9281 obese subjects who had not taken appetite suppressants who were matched to the treated subjects for age, sex, and weight. All subjects were free of diagnosed cardiovascular disease at the start of follow-up. The average duration of follow-up for all subjects was about four years. RESULTS: There were 11 cases of newly diagnosed idiopathic valvular disorders, 5 after the use of dexfenfluramine and 6 after the use of fenfluramine. There were six cases of aortic regurgitation, two cases of mitral regurgitation, and three cases of combined aortic and mitral regurgitation. There were no cases of idiopathic cardiac-valve abnormalities among the subjects who had not taken appetite suppressants or among those who took only phentermine. The five-year cumulative incidence of idiopathic cardiac-valve disorders was 0 per 10,000 subjects among those who had not taken appetite suppressants (95 percent confidence interval, 0 to 15.4) and among those who took phentermine alone (95 percent confidence interval, 0 to 76.6), 7.1 per 10,000 subjects among those who took either fenfluramine or dexfenfluramine for less than four months (95 percent confidence interval, 3.6 to 17.8; P=0.02 for the comparison with subjects who had not taken appetite suppressants), and 35.0 per 10,000 subjects among those who received either of these medications for four or more months (95 percent confidence interval, 16.4 to 76.2; P<0.001). CONCLUSIONS: The use of fenfluramine or dexfenfluramine, particularly for four months or longer, is associated with an increased risk of newly diagnosed cardiac-valve disorders, particularly aortic regurgitation.     

Weakness of biochemical markers of nutritional and inflammatory status as prognostic indices for growth retardation and morbidity of young children in central Africa

BACKGROUND: Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss. METHODS: We screened 773 nonpregnant women who had the unexplained loss of at least two fetuses for antinuclear, anti-DNA, antilymphocyte, and anticardiolipin antibodies and for the lupus anticoagulant. Of 385 women with at least one autoantibody, 202 who later became pregnant were randomly assigned in equal numbers to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy. The women were stratified according to age (18 to 34 years or 35 to 39 years) and the week of gestation at which the previous fetal losses had occurred (< or = 12 or > 12 weeks). The primary outcome measure was a successful pregnancy. RESULTS: Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02). CONCLUSIONS: Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.     

Effect of the evaluation parameter on sensitivity of resonance thrombography of thrombocytopenia in dogs

Based on 109 blood samples taken from 36 dogs suffering from thrombocytopenia resonance thrombography with the resonance thrombograph RTG 801 (von Hoerner und Sulger Electronic GmbH, Schwetzingen; manufacturer: Fresenius AG, Bad Homburg) was distinctly more sensitive and more closely correlated to the platelet count using an optimized parameter of the resonance thrombogramm (RTG) in comparison to usual parameters. Nevertheless, clinical requirements regarding samples with platelet counts > 25,000/microliter were not fulfilled. Out of 13 samples with reduced platelet count and simultanous extended capillary bleeding time, depending on the used parameter a maximum of 9 samples could be detected as pathological by the RTG. The normal RTG in part of the cases with clearly altered primary haemostasis contrasts to the exclusive use of RTG in the screening of thrombocytopenia in dogs.     

Heparin-induced thrombocytopenia and thrombosis: presentation after cardiopulmonary bypass

Heparin-induced thrombocytopenia and thrombosis syndrome was diagnosed in a 63-year-old woman 11 days after coronary artery bypass grafting. Her only presenting complaints were incisional leg pain and vague chest discomfort. The syndrome was suspected when her platelet count was found to be 37,000/microL. A subsequent ventilation-perfusion lung scan showed findings highly probable for pulmonary embolism. An inferior venacavogram obtained before a pulmonary angiogram revealed a large retrohepatic thrombus at the right atrial junction. The patient was successfully treated with the defibrinogenating agent ancrod (Arvin). A diagnosis of heparin-induced thrombocytopenia and thrombosis syndrome should be considered and heparin therapy should be avoided in patients with low platelet counts who have been previously treated with heparin.     

A multicenter trial of two dexamethasone regimens in ventilator-dependent premature infants

BACKGROUND: Ventilator-dependent premature infants are often treated with dexamethasone. However, the optimal timing of therapy is unknown. METHODS: We compared the benefits and hazards of initiating dexamethasone therapy at two weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth-weight infants (501 to 1500 g) who had respiratory index scores (mean airway pressure x the fraction of inspired oxygen) of 52.4 at two weeks of age. One hundred eighty-two infants received dexamethasone for two weeks followed by placebo for two weeks, and 189 infants received placebo for two weeks followed by either dexamethasone (those with a respiratory-index score of > or =2.4 on treatment day 14) or additional placebo for two weeks. Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five days, and the dose was then tapered. RESULTS: The median time to ventilator independence was 36 days in the dexamethasone-placebo group and 37 days in the placebo-dexamethasone group. The incidences of chronic lung disease (defined as the need for oxygen supplementation at 36 weeks' postconceptional age) were 66 percent and 67 percent, respectively. Dexamethasone was associated with an increased incidence of nosocomial bacteremia (relative risk, 1.5; 95 percent confidence interval, 1.1 to 2.1) and hyperglycemia (relative risk, 1.9; 95 percent confidence interval, 1.2 to 3.0) in the dexamethasone-placebo group, elevated blood pressure (relative risk, 2.9; 95 percent confidence interval, 1.2 to 6.9) in the placebo-dexamethasone group, and diminished weight gain and head growth (P< 0.001) in both groups. CONCLUSIONS: Treatment of ventilator-dependent premature infants with dexamethasone at two weeks of age is more hazardous and no more beneficial than treatment at four weeks of ages.     

Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994

BACKGROUND AND METHODS: To clarify the determinants of contemporary trends in mortality from coronary heart disease (CHD), we conducted surveillance of hospital admissions for myocardial infarction and of in-hospital and out-of-hospital deaths due to CHD among 35-to-74-year-old residents of four communities of varying size in the United States (a total of 352,481 persons in 1994). Between 1987 and 1994, we estimate that there were 11,869 hospitalizations for myocardial infarction (on the basis of 8572 hospitalizations sampled) and 3407 fatal coronary events (3023 sampled). RESULTS: The largest average annual decrease in mortality due to CHD occurred among white men (change in mortality, -4.7 percent; 95 percent confidence interval, -2.2 to -7.1 percent), followed by white women (-4.5 percent; 95 percent confidence interval, -0.7 to -8.2 percent), black women (-4.1 percent; 95 percent confidence interval, -10.3 to +2.5 percent), and black men (-2.5 percent; 95 percent confidence interval, -6.9 to +2.2 percent). Overall, in-hospital mortality from CHD fell by 5.1 percent per year, whereas out-of-hospital mortality declined by 3.6 percent per year. There was no evidence of a decline in the incidence of hospitalization for a first myocardial infarction among either men or women; in fact, such hospital admissions increased by 7.4 percent per year (95 percent confidence interval for the change, +0.5 to +14.8 percent) among black women and 2.9 percent per year (95 percent confidence interval, -3.6 to +9.9 percent) among black men. Rates of recurrent myocardial infarction decreased, and survival after myocardial infarction improved. CONCLUSIONS: From 1987 to 1994, we observed a stable or slightly increasing incidence of hospitalization for myocardial infarction. Nevertheless, there were significant annual decreases in mortality from CHD. The decline in mortality in the four communities we studied may be due largely to improvements in the treatment and secondary prevention of myocardial infarction.