Evidence-based medicine as a tool for clinical decision-making in Puerto Rico

Evidence-based medicine (EBM) is defined as "the process of systematically finding, appraising and using contemporaneous research findings as the basis for clinical decisions". Although EBM has been extensively described across the Americas and Europe, no study has looked at the practice of EBM in Puerto Rico. A cross-sectional analysis based on a 23-item questionnaire was employed. We showed that there is a high use (88%) and familiarity (93%) with EBM, and that physicians keep a positive attitude towards EBM (80%) in Puerto Rico. There is an over-representation of academicians (58.9% vs. 34.6%, p = 0.02) and an under-representation of solo office practitioners (10.5% vs. 26.9%, p = 0.03) among EBM users. Additionally, patient workload (48%), time constraints (36%), and limited access to the Internet (28%) were the most frequently cited obstacles to the practice of EBM in Puerto Rico. Taken together, these results help create a cross-sectional profile of EBM practice among Puerto Rican physicians.

Early diagnosis of trophoblast produced capillary hypertension (pregnancy-induced hypertension).

A clinical study was initiated to demonstrate that blood pressure in the capillaries increases long before there is a rise in arterial blood pressure. Thus the diagnosis of capillary hypertension can be made much earlier, even before gross tissue edema is observed. Bearing in mind the pathogenetic mechanism of the development of pregnancy-induced hypertension (PIH) complicating the clinical picture, analyzed hematocrit had great statistical significance. Also, by following the diagnostic sequence, after hematocrit, Acidum uricum shows pathologic and protein loss values. Clinical application of this study would be in timely albumin administration and fast oncotic pressure regulation in order to avoid hypertension complications.

Reduction in the cesarean section rate in nulliparous patients after administration of intravenous propranolol.

OBJECTIVE: A preliminary investigation to test the efficacy of intravenous propranolol in reducing the cesarean section rate in nulliparas in active labor and evaluate its effect on neonatal and maternal outcomes. METHODS: Fifty seven nulliparous patients admitted in active labor were randomly divided into two groups: a control group consisting of 23 patients, and a treatment group consisting of 34 patients given 2 mg of propranolol intravenously every 4 hours until delivery. Total length of labor, time from first administration of medication to delivery, incidence of cesarean section, APGAR scores, maternal and fetal morbidity were assessed. RESULTS: A total of 4 cesarean sections were performed in each group (11.7% in the treatment group and 17.3% in the control group). The rate of cesarean section due to dystocia was 6.25 and 13.6% respectively (P = .367). Statistical significance was not reached due to the small number of subjects (students t test analysis). There was no increase in the incidence of low APGAR scores, intensive care unit admissions, abnormal heart rate patterns during labor, cesarean sections for fetal distress or maternal morbidity in the treated group. CONCLUSIONS: Intravenous administration of 2 mg of propranolol every four hours is safe and not associated to increased neonatal or maternal morbidity. A 50% decrease in the incidence of cesarean sections can be documented among nulliparous patients treated with propranolol although the small numbers and overall low incidence of cesarean section in our population (14%) did not permit these differences to reach statistical significance.

Effect of prenatal T4 treatment in neonatal morbidity: preliminary findings.

We report our experience with the use of intra-amniotic thyroxine to accelerate fetal maturation in preterm delivered infants. One hundred and fourteen infants who had received 500 micrograms of thyroxine weekly prenatally until an L/S ratio greater or equal to 2.0 was achieved, were compared to 113 premature infants who had not been given thyroxine or steroids prenatally. After stratification by weight, the relative incidence of respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC) and intraventricular hemorrhage (IVH) were compared. A decrease in the incidence of RDS was observed in the infants with birth weight between 1000 and 1500 g who had received more than one dose of intra-amniotic thyroxine. No difference in the incidence of RDS was observed in infants with birth weight of less than 1000 g or over 1500 g. One dose of thyroxine had no effect in decreasing the incidence of RDS, PDA, NEC, and IVH in any of the groups. We conclude intra-amniotic thyroxine seems to decreases the incidence of RDS in very low birth weight infants.

Effect of prenatal T4 treatment in neonatal morbidity: preliminary findings

We report our experience with the use of intra-amniotic thyroxine to accelerate fetal maturation in preterm delivered infants. One hundred and fourteen infants who had received 500 micrograms of thyroxine weekly prenatally until an L/S ratio greater or equal to 2.0 was achieved, were compared to 113 premature infants who had not been given thyroxine or steroids prenatally. After stratification by weight, the relative incidence of respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC) and intraventricular hemorrhage (IVH) were compared. A decrease in the incidence of RDS was observed in the infants with birth weight between 1000 and 1500 g who had received more than one dose of intra-amniotic thyroxine. No difference in the incidence of RDS was observed in infants with birth weight of less than 1000 g or over 1500 g. One dose of thyroxine had no effect in decreasing the incidence of RDS, PDA, NEC, and IVH in any of the groups. We conclude intra-amniotic thyroxine seems to decreases the incidence of RDS in very low birth weight infants

Comparison of the endocervical brush and the endocervical curettage for the evaluation of the endocervical canal.

OBJECTIVE: To evaluate and compare the efficacy in obtaining an adequate endocervical sampling using the endocervical brush and the endocervical curettage. METHODS: Analysis of the cytology and histology of samples obtained from patients referred to the University of Puerto Rico School of Medicine Tertiary Care Center Anaplasia Clinics for colposcopy due to an abnormal Pap smear having atypical cells or higher as classified according to the Bethesda System. All patients underwent evaluation of the endocervical canal with an endocervical brush and an endocervical curettage. RESULTS: Fifty three of fifty-eight patients had correlating endocervical brush Papanicolaou smear and endocervical curettage. Only five patients presented discrepancies. All endocervical brush samples had sufficient tissue for diagnosis. CONCLUSION: The endocervical curettage is operator dependent, is difficult to perform in patients with a stenotic cervical os or in menopausal patients. The endocervical brush is easier to use, malleable and has a lower processing cost. In view of these findings evaluation of the endocervix can be safely performed with the use of an endocervical brush. When used properly, the endocervical brush has a sensitivity of 90%, a specificity of 92.1% and a positive predictive value of 87.5%.

Amniotic fluid epidermal growth factor concentrations. The effect of intra-amniotic thyroxine for acceleration of fetal maturation.

Intra-amniotic thyroxine (200-500 ug) was administered weekly to 29 women in the third trimester to enhance fetal maturation. Lecithin-sphingomyelin ratio (L/S) and epidermal growth factor (EGF) were measured in amniotic fluid (AF) before (n = 58) and after (n = 92) administration of thyroxine. The AF L/S ratio and EGF concentration increased linearly with increasing gestational age both before (r = 0.76, p < 0.0001; r = 0.41, p < 0.001, respectively) and after (r = 0.62, p < 0.0001; r = 0.43, p < 0.001 respectively) initiation of thyroxine treatment. The slopes of gestational age vs L/S (0.07) and EGF (0.004) before T4 increased significantly after initiation of T4 therapy (L/S:0.23, p < 0.001; EGF:0.015, p < 0.01, respectively). L/S ratios correlated with AF EGF levels before (r = 0.77, p < 0.001) and after (r = 0.63, p < 0.001) initiation of T4 therapy. These results demonstrate that intra-amniotic thyroxine accelerates not only the progression of the amniotic fluid L/S ratio, but the appearance of EGF.

Misreporting of maternal mortality in Puerto Rico.

Maternal mortality (MM) continues to be a problem that plagues many developed and underdeveloped countries around the world. It has been estimated that the minimum amount of underreporting in the U.S. to be 20%, resulting in MM rates that may be substantially higher than reported. The national goal for the MM for the year 1990 has been set at 5/100,000, and at the present trend it is expected that this may be achieved among the white population, but not among minorities. P.R. reported a maternal mortality rate of 5/100,000 in 1975. It was suspected that such a low rate was due to underreporting, a study was undertaken to investigate that possibility. The results indicated that there was severe underreporting of maternal deaths during 1978 = 79. Recently, there has been a growing concern that the level of underreporting in PR continues to be high. Since there has been no evidence that the surveillance has improved, the Dept. of Health requested from the Dept. of Ob-Gyn of the University of Puerto Rico Medical School and the Dept. of Maternal and Child Health to conduct a study to find out if the previous findings held true for recent years. The study was based on the review of selected medical records corresponding to deaths of women of childbearing age whose causes of death, as coded in the death certificate, were considered as having a high probability of masking a misreported maternal death. It was decided to investigate those deaths occurring in 1982, to see if the results of the previous study had caused any impact on the surveillance of maternal deaths in Puerto Rico.

Responsiveness of L-S ratio of the amniotic fluid to intra-amniotic administration of thyroxine. Role of fetal age.

Since 1982 we have accelerated fetal maturation with intra-amniotic thyroxine (T4) in more than 140 patients. The purpose of this analysis was to determine the rate of change of the ratio of lecithin to sphingomyelin (L/S) after administration of T4 at different gestational ages, and to compare the responses to the first and the second administration of T4. Fifty-nine cases in which administration of T4 was continued for 2 weeks or more, and in which at least 3 determinations of L/S had been performed, were identified. Gestational age of the fetus at the inititiation of treatment ranged from 26 to 31 weeks (mean 29.3 weeks). Thyroxine was administered weekly in 200 to 500 mcg doses. Administration of T4 prior to the 27th week did not change the L/S. From the 27th and 31st week of gestation, the slope of the L/S, after the initial dose of T4 increased from 0.33/wk to 1.05/wk. In contrast the slope of the untreated patients changed little reaching a maximum of 0.22 at the 33 week. L/S greater than 2 was observed in 80% of cases after 2 weeks of therapy, when it had been initiated after the 26th week. The response to the second dose was about twice that of the first in fetuses less than or equal to 30 weeks, but was similar to that seen after the initial dose in fetuses greater than 30 weeks. Phosphatidylglycerol (PG) was detected in amniotic fluid in 51% of cases after 2 weeks of treatment, and in 6 instances as early as at the 30th week. Responsiveness of L/S to T4 treatment of the fetus is a function of gestational age and of prior exposure to T4.

Acceleration of fetal maturation with intra-amniotic thyroxine in the presence of maternal malignancy.

Acceleration of fetal maturation with intra-amniotic administration of thyroxine was employed in eight patients in whom preterm delivery was necessary because of malignant disease of the mother. Thyroxine (200 mcg to 500 mcg) was given at weekly intervals starting at the 27th to 32nd week of gestation until the L-S ratio exceeded 2.0. The fetuses were delivered between the 29.4 and 34.0 week. None of the newborns suffered from respiratory distress syndrome, and three newborns were cared for in the regular nursery. Thyroxine-induced acceleration of fetal maturation and pre-term delivery permits earlier initiation of antineoplastic and radiation therapy without exposing the fetus to the hazards of maternal therapy and those of prematurity.

Single cause for initiation of labor and toxemia: a hypothesis.

A hypothesis is presented that states that the decline in oxygen tension (PO2) in the intervillous space causes both toxemia (preeclampsia-eclampsia) and the initiation of labor. The trophoblast is identified as the monitor of the fetal PO2 and as the source of substances that are released into the maternal circulation stimulating the myometrium, the heart, the vascular smooth muscle, and, perhaps, the brain. In the presence of normal trophoblast the release takes place only when the PO2 in the intervillous space decreases to a level at which the fetus should be expelled from the uterus to avoid intrapartum hypoxia. Near term, the myometrium is the most responsive site to the released substances, and stimulation of the heart and systemic vasculature is observed only infrequently. With release of these substances, intrapartum toxemia results. Toxemia before onset of labor is created by hypoxia of the trophoblast in the presence of a nonresponsive myometrium to materials released. A small placenta, compression of the intervillous space by villous edema, and avulsion of spiral arterioles are the main causes of the premature decline of intervillous space PO2, leading to toxemia. Postpartum toxemia is produced by the retained (extraplacental) trophoblast, perhaps facilitated by the rapid clearance of progesterone.

Papillary adenocarcinoma in the endometrium.

Papillary adenocarcinoma should be regarded as a subtype of endometrial carcinoma with poor prognosis. Review of 22 cases indicates an older average age than is found with the usual endometrioid type, with frequent surgical upstaging, deep myometrial invasion, nodal and adnexal involvement, positive peritoneal washings, upper abdominal recurrence, and poor response to conventional treatment. These observations suggest a different natural history from that of the more common histologic subtypes of endometrial carcinoma. Management should include initial exploration of the entire abdominal cavity to determine the true extent of the disease, and treatment must include the upper abdomen.

Ruptured chordae tendineae complicating pregnancy. A case report.

A 29-year-old women at 30 weeks' gestation had acute mitral insufficiency secondary to bacterial endocarditis and ruptured chordae tendineae. Although this complication has been reported on previously, recent advances in technology have led to significant improvements in its diagnosis and treatment.

Fetal heart rate and blood pressure during prolonged partial asphyxia in the rhesus monkey.

Fetal heart rate (FHR) and fetal blood pressure (FBP) were recorded continuously in 20 anesthetized fetal monkeys near term while their oxygenation was progressively decreased by a stepwise reduction in uterine blood flow. Fetal blood was sampled periodically from the carotid artery and analyzed for pH and PO2. Hemoglobin saturation with oxygen (S) was derived from nomogram. During the study period, uterine contractions were either minimal or absent. FHR remained constant as long as S was greater than 55%. Below that it began to decline by 0.34%/% saturation. When S was less than 31%, FHR fell by 0.93%/% saturation. The correlation between FHR and PO2, and FHR and pH, was less consistent. Arterial FBP was maintained over the entire range of pH, PO2, and S. It is concluded that, under the conditions described, an unequivocal decrease in mean FHR signals a substantial reduction in the availability of O2 to the fetus.

Cryoenzymology and spectrophotometry of pea seedling diamine oxidase.

Diamine oxidase follows bi-ter ping-pong kinetics, with an intermediate, "reduced" free-enzyme form being generated after the anaerobic conversion of amine to aldehyde. Visible spectra of diamine oxidase reacting at subzero temperatures provide evidence that this intermediate enzyme form is obtained via several other intermediates and that the environment of the Cu(II) changes dramatically during the course of the reaction [even though it is not reduced to Cu(I) during the catalytic cycle]. The spectrum of this form of diamine oxidase, which is obtained 0.5--2 h after the addition of amine at -5 to -15 degrees C, is independent of substrate, is identical with that obtained by anaerobic addition of substrate at room temperature, and provides evidence for a direct interaction of Cu(II) with the organic cofactor of the enzyme. This interaction is apparently charge transfer in nature. Upon removal of Cu(II) from the native enzyme, one obtains spectral evidence that the organic cofactor is still present. However, removal of the Cu(II) from the reduced (intermediate) enzyme form yields a featureless enzyme spectrum and a Cu(II)--chelate complex which contains a new ligand, which is presumably the second prosthetic group.