[Pharmacovigilance in a paediatric intensive care unit]. / Original Breve Farmacovigilancia en una unidad de cuidados intensivos pediátricos.

OBJECTIVE: To analyze suspected drug-related adverse events as reported by pharmacists in a pediatric intensive care unit. METHOD: Suspected drug-related adverse events were recorded as reported by pharmacists in an intensive care unit during hospital rounds (these were neither systematic nor continued) or patient visits to our clinic (April 2004-May 2005). Later on, the pharmacovigilance subcommittee prospectively analyzed such suspected events in order to confirm them and classify them according to their rules. RESULTS: Nineteen suspected adverse events were reported for 17 patients; 15 were confirmed (78%). In six cases the pharmacist suggested the way the adverse event was eventually treated. Three cases required admission to an ICU. Drug classes most commonly involved included antimicrobials, anti-epileptic drugs, and immunosuppressants. Severity was: fatal 20%, serious 34%, moderate 13%, mild 33%. Causality was definitely established for 13%, probable for 54%, and possible for 33% of patients; 20% of events were considered avoidable. CONCLUSIONS: Adverse events reported by pharmacists were few, as they could not attend hospital rounds on a regular basis. Imputability was difficult due to critical patient conditions. Most suspected events were later confirmed. Treatment involved therapy adjustments according to individual patient characteristics.

Dopamine receptors in the brains of schizophrenia patients: a meta-analysis of the findings.

Controversy surrounds the question of whether there are dopamine (DA) receptor abnormalities in the brains of schizophrenia patients; in particular, whether DA receptors of the D2 family are elevated in density. Methodological factors and sample characteristics have been postulated to account for differences in study outcome, but there has been no systematic analysis of the contribution of these factors to study effect sizes. This meta-analysis of the research findings sought to determine the influence of methodologic factors and sample characteristics on the magnitude of diagnostic group differences in DA D2 density (Bmax) and affinity (Kd). The analysis suggests at least moderate effects, such that schizophrenia patients show an elevation in both values when compared to controls. These effects are amplified in medicated patients, but not solely attributable to antipsychotics. The group differences in DA D2 receptor density and affinity increase with age among nonmedicated patients. The use of a butyrophenone ligand also yields larger effects. It is concluded that a subgroup of schizophrenia patients manifests increased DA D2 receptor density and decreased receptor affinity. In the absence of medication, these changes may become more pronounced with age. Differences in study outcome are also partially due to methodologic factors, including the ligand.

Are the etiologies of cervical and trochanteric hip fractures different?

Review of results published in the past few years indicates that there are several differences between women sustaining trochanteric fractures of cervical hip fractures. In most series women with trochanteric fractures are older, shorter, and lighter than those with cervical fractures. The bone mineral density was found to be lower in trochanteric fractures, but although in the majority of the studies the diminution was statistically significant at the level of the trochanter and spine--with predominant trabecular bone--the decrease was not uniformly significant at the level of the femoral neck or total skeleton. Previous vertebral fractures were twice as common in patients with trochanteric fractures. Ultrasound exploration of the calcaneus disclosed that the values were significantly lower in women with trochanteric fractures and this finding was independent of the diminution of the bone mineral density. On the other hand, fall biomechanics have not been found to be different in the two types of hip fractures. In summary, women with trochanteric fractures have a more severe and generalized bone loss, especially of the trabecular component. Cervical fractures seem to be more related to pelvic structure-failure of the outer diameter of the femoral neck to expand with age and increased acetabular bone width-added to a focal bone loss. The two main types of fractures should be treated separately in epidemiological or clinical studies to increase the knowledge and the possibilities of preventing hip fractures.

[Proximal femoral fractures: risk factors, bone mineral density, body composition and biochemical changes in and age-matched patients and controls]. / Fracturas del fémur proximal: factores de riesgo, densidad mineral osea, composición corporal y alteraciones bioquímicas en pacientes y controles de similar edad.

During one year (6/93-5/94) we performed a prospective study in patients with hip fracture, treated at the Hospital de Clínicas. A total of 102 women 52 to 94 years of age (Mean +/- 1SD: 79.5 +/- 9.1 years) and 17 men 61 to 98 years of age (79.7 +/- 9.9 years) who had sustained a hip fracture due to mild or moderate trauma were included. The ratio women: men was 6:1. We also studied 55 age-matched control women without diseases that could affect the skeleton or previous hip fracture (77.1 +/- 5.8 years of age). We did not study a control group in men. Women with hip fractures had lower weight (p < 0.01), lower age of onset of the menopause (p < 0.01) and a tendency to have with a greater frequency a mother with hip fracture (p < 0.08) compared with age-matched controls. When vertebral fractures were excluded, 44% of the hip fracture women had sustained previous skeletal fractures, while only 16% of the age-matched controls had suffered previous skeletal fractures (p < 0.001) (Table 2). The most frequent previous skeletal fractures were wrist and humerus. Forty eight percent of hip fracture women had had at least one vertebral fracture. About 17% of the hip fractured men had sustained previous skeletal fractures, while 5/12 men had suffered at least one vertebral fracture. Hip fractured women and men sustained greater history of diseases which provoke postural instability (Table 3). Biochemical determinations showed significantly diminished levels of serum albumin (p < 0.001) and calcium (p < 0.01), and increased serum PTH (p < 0.05) compared to age-matched controls (Table 4). Bone mineral density (determined by dual energy X-ray absorptiometry) was significantly diminished over proximal femur, total skeleton, legs and pelvis (p < 0.001), head and spine (p < 0.05) (Table 5). Body composition measurements showed that hip fracture women had a significantly lower lean mass compared with controls (p < 0.05). Fat mass also was lower in fracture patients compared with controls, but the difference was not statistically significant (Table 5). We conclude that hip fracture in our population is related to several previous factors: earlier onset of menopause, lower nutrition and body weight, previous diseases that increase the likelihood of falling, increased levels of PTH and reduced bone mass. Prevention of hip fractures should take into account all these factors, specially those that could be modified.

Influence of the menopausal age on the severity of osteoporosis in women with vertebral fractures.

To assess the effect of age at the onset of menopause over the skeleton we have determined the age and cause of menopause and bone mineral density (BMD), by dual and single photon absorptiometry of the lumbar spine, the proximal femur and the radius shaft on 1050 osteoporotic women (suffering with at least one atraumatic vertebral fracture). The mean +/- 1 S.D. menopausal age was 47.1 +/- 7.6 years. The onset of menopause occurred prior to age 45 in 22% (premature), after age 52 in 9% (late), and between 45 and 52 years of age in 69% (normal menopausal age). When the osteoporotic women were categorized into three groups according to the age of menopause, those osteoporotic with premature menopause had a significantly greater frequency of hip fractures, a significantly lower age, weight and BMD over the spine, proximal femur and radius shaft compared with those of normal menopausal age. In turn, patients with late menopause had a significantly increased weight and BMD over the spine. These findings indicate that among patients with vertebral osteoporosis those women with premature menopause had a more severe bone loss and a significantly greater frequency of hip fractures.

Intravenous pamidronic acid in hypercalcemia due to parathyroid carcinoma.

Three patients aged between 31 and 59 were treated with pamidronic acid (APD) due to severe hypercalcemia caused by parathyroid carcinoma. APD was given in 250 cm3 intravenous saline over a 2 h period in a dose of 0.45 to 0.50 mg/kg per day. Two patients received 6 and the other 9 infusions. Mean serum calcium diminished from 15.7 +/- 1.3 mg/dl to 11.7 +/- 0.6 mg/dl (p less than 0.05). Mean serum ionized calcium decreased from 8.1 mg/dl to 5.5 mg/dl, urinary calcium excretion from 478 mg/24 h to 229 mg/24 h and hydroxyproline from 204 mg/24 h to 117 mg/24 h. Serum calcium returned to pretreatment levels after 5 and 15 days post intravenous APD in two patients. In the third patient treated with 900 mg/day of oral APD, after the intravenous therapy the relapse occurred during the fourth month. The three patients received a second course of intravenous (iv) APD. The effect upon serum calcium (14.6 +/- 1.1 mg/dl to 11.8 +/- 0.6 mg/dl, p less than 0.05) was similar to the one obtained with the first course. Intravenous APD administration appears to be an effective and safe treatment of the severe hypercalcemia due to parathyroid carcinoma. To sustain levels of serum calcium attained in patients with non resectable tumors, a suitable program of iv APD pulses should be established.

Intravenous pamidronic acid in hypercalcemia due to parathyroid carcinoma

Tres pacientes, entre 31 y 59 años de edad, recibieron Pamidronato (APD) debido a que presentaban una hipercalcemia severa, causada por un carcinoma de paratiroides. El APD fue administrado en 250 cm3 de solución salina por vía endovenosa, durante un período de 2 horas, en una dosis entre 0.45 a 0.50 mg/Kg/día. Dos de los pacientes recibieron 6 y el restante 9 infusiones. La calcemia promedio disminuyó de 15.7 ñ 1.3 mg/dl a 11.7 ñ 0.6 mg/dl (p < 0.05). El calcio iónico promedio descdendió de 8.1 mg/dl a 5.5 mg/dl, la excreción urinaria de calcio de 478 g/24 hs a 229 mg/24 hs y a hidroxiprolina urinaria de 204 mg/24 hs a 117 mg/24 hs. El 2 pacientes la calcemia retornó a valores similares al pretratamiento 5 y 15 días después de suspender las infusiones endovenosas de APD. En el tercer paciente, tratado con APD por vía oral (900 mg/día) después de la terapia endovenosa, la recidiva de la hipercalcemia ocurrió durante el cuarto mes. Los tres pacientes recibieron un segundo curso de APD endovenoso. La disminución de la calcemia (14.6 ñ 1.1 mg/dl a 11.8 ñ 0.6 mg/dl; p < 0.05) fue similar a la obtenida con el primer curso de tratamiento. La administración endovenosa de APD fue efectiva en el control de la hipercalcemia severa debida al carcinoma de paratiroides. En aquellos pacientes con tumores que no pueden ser tratados quirúrgicamente, para mantener los niveles de calcemia obtenidos con el tratamiento agudo, un programa de administración intermitente de APD endovenoso debe ser investigado

Intravenous pamidronic acid in hypercalcemia due to parathyroid carcinoma.

Three patients aged between 31 and 59 were treated with pamidronic acid (APD) due to severe hypercalcemia caused by parathyroid carcinoma. APD was given in 250 cm3 intravenous saline over a 2 h period in a dose of 0.45 to 0.50 mg/kg per day. Two patients received 6 and the other 9 infusions. Mean serum calcium diminished from 15.7 +/- 1.3 mg/dl to 11.7 +/- 0.6 mg/dl (p less than 0.05). Mean serum ionized calcium decreased from 8.1 mg/dl to 5.5 mg/dl, urinary calcium excretion from 478 mg/24 h to 229 mg/24 h and hydroxyproline from 204 mg/24 h to 117 mg/24 h. Serum calcium returned to pretreatment levels after 5 and 15 days post intravenous APD in two patients. In the third patient treated with 900 mg/day of oral APD, after the intravenous therapy the relapse occurred during the fourth month. The three patients received a second course of intravenous (iv) APD. The effect upon serum calcium (14.6 +/- 1.1 mg/dl to 11.8 +/- 0.6 mg/dl, p less than 0.05) was similar to the one obtained with the first course. Intravenous APD administration appears to be an effective and safe treatment of the severe hypercalcemia due to parathyroid carcinoma. To sustain levels of serum calcium attained in patients with non resectable tumors, a suitable program of iv APD pulses should be established.

Intravenous pamidronic acid in hypercalcemia due to parathyroid carcinoma

Tres pacientes, entre 31 y 59 años de edad, recibieron Pamidronato (APD) debido a que presentaban una hipercalcemia severa, causada por un carcinoma de paratiroides. El APD fue administrado en 250 cm3 de solución salina por vía endovenosa, durante un período de 2 horas, en una dosis entre 0.45 a 0.50 mg/Kg/día. Dos de los pacientes recibieron 6 y el restante 9 infusiones. La calcemia promedio disminuyó de 15.7 ñ 1.3 mg/dl a 11.7 ñ 0.6 mg/dl (p < 0.05). El calcio iónico promedio descdendió de 8.1 mg/dl a 5.5 mg/dl, la excreción urinaria de calcio de 478 g/24 hs a 229 mg/24 hs y a hidroxiprolina urinaria de 204 mg/24 hs a 117 mg/24 hs. El 2 pacientes la calcemia retornó a valores similares al pretratamiento 5 y 15 días después de suspender las infusiones endovenosas de APD. En el tercer paciente, tratado con APD por vía oral (900 mg/día) después de la terapia endovenosa, la recidiva de la hipercalcemia ocurrió durante el cuarto mes. Los tres pacientes recibieron un segundo curso de APD endovenoso. La disminución de la calcemia (14.6 ñ 1.1 mg/dl a 11.8 ñ 0.6 mg/dl; p < 0.05) fue similar a la obtenida con el primer curso de tratamiento. La administración endovenosa de APD fue efectiva en el control de la hipercalcemia severa debida al carcinoma de paratiroides. En aquellos pacientes con tumores que no pueden ser tratados quirúrgicamente, para mantener los niveles de calcemia obtenidos con el tratamiento agudo, un programa de administración intermitente de APD endovenoso debe ser investigado (AU)