Utilización de medicamentos en condiciones off-label y unlicensed: resultados de un estudio piloto realizado en una unidad de cuidados intensivos pediátricos / Off-label and unlicensed drug use: Results from a pilot study in a pediatric intensive care unit

OBJETIVO: Evaluar el perfil de utilización de medicamentos en situaciones no autorizadas en una unidad de cuidados intensivos pediátricos de un hospital universitario. MÉTODOS: Se realizó un estudio observacional descriptivo prospectivo durante 6 semanas en una unidad de cuidados intensivos pediátricos. Se incluyeron pacientes ingresados con edades entre 0-18 años. Se evaluó cada uno de los medicamentos prescritos, indicación o condición de uso, según la información reflejada en las fichas técnicas autorizadas por la Agencia Europea de Medicamentos. Se definió un algoritmo secuencial para clasificar de manera estandarizada los medicamentos según la condición de prescripción en unlicensed, off-label o aprobado. RESULTADOS: Se incluyeron 42 pacientes, analizándose un total de 696 prescripciones, que implicaron 102 fármacos diferentes. Todos los pacientes tuvieron al menos un tratamiento off-label. El 8,6% del total de tratamientos analizados se utilizaron en condiciones unlicensed y el 53,9% en off-label. El principal motivo de uso off-label fue por indicación, seguido de la edad y dosis. Existe una relación lineal entre frecuencia de uso de medicamentos en condiciones off-label y la edad del paciente, aumentando esta frecuencia según disminuye la edad del paciente. Los medicamentos más utilizados en condiciones off-label fueron: atropina, etomidato, metamizol y ranitidina, y en condiciones unlicensed fueron: espironolactona, sildenafilo, acetazolamida e hidroclorotiazida. CONCLUSIÓN: La unidad de cuidados intensivos pediátricos se caracteriza por una alto ratio de medicamentos prescritos en condiciones no autorizadas. La realización de estudios de estas características permite documentar la práctica clínica respecto al uso de medicamentos en condiciones distintas a las autorizadas

PURPOSE: To analyze the prevalence of use of off-label and unlicensed drugs in a pediatric intensive care unit of a University Hospital. METHOD: An observational, descriptive, prospective six week pilot study in a Pediatric Intensive Care Unit. Hospitalized patients aged between 0 and 18 years were included. Each prescribed drug was evaluated taking into account indication and condition of use, according to the information available on the Summary of Product Characteristics established by the European Medicines Agency. A sequential algorithm was defined allowing drug classification in unlicensed, off-label or approved. RESULTS: Forty-two patients were included. A total of 696 prescriptions, involving 102 different drugs, were analyzed. All patients had at least one off-label prescription, and a median of 8.9 off-label prescriptions was obtained. Of the total prescriptions, 8.6% were unlicensed and 53.9% corresponded to off-label use. The main reason for off-label use was by indication, followed by age and dose. A lineal tendency between off-label drug use and patient age was observed, where off-label use increased as patient age decreased. The drugs most commonly used offlabel were: atropine, etomidate, dipyrone and ranitidine, and unlicensed drugs: spironolactone, sildenafil, acetazolamide and hydrochlorothiazide. CONCLUSION: Pediatric Intensive Care Units are characterized by a high ratio of off-label and unlicensed prescriptions. The scarce number of studies performed in this specific and complex sub-population added inconveniency to the current lack of data on safety and efficacy for drugs in paediatrics. Performing studies with these characteristics allows us to document practice on paediatric drug utilisation are required

Healthcare-associated infections in neonatal units: lessons from contrasting worlds.

Neonatal intensive care units are vulnerable to outbreaks and sporadic incidents of healthcare-associated infections (HAIs). The incidence and outcome of these infections are determined by the degree of immaturity of the neonatal immune system, invasive procedures involved, the aetiological agent and its antimicrobial susceptibility pattern and, above all, infection control policies practised by the unit. It is important to raise awareness of infection control practices in resource-limited settings, since overdependence upon antimicrobial agents and co-existing lack of awareness of infection control is encouraging the emergence of multi-drug-resistant nosocomial pathogens. We reviewed 125 articles regarding HAIs from both advanced and resource-limited neonatal units in order to study risk factors, aetiological agents, antimicrobial susceptibility patterns and reported successes in infection control interventions. The articles include surveillance studies, outbreaks and sporadic incidents. Gram-positive cocci, viruses and fungi predominate in reports from the advanced units, while Gram-negative enteric rods, non-fermenters and fungi are commonly reported from resource-limited settings. Antimicrobial susceptibility patterns from surveillance studies determined the empirical therapy used in each neonatal unit. Most outbreaks, irrespective of the technical facilities available, were traced to specific lack of infection control practices. We discuss infection control interventions, with special emphasis on their applicability in resource-limited settings. Cost-effective measures for implementing these interventions, with particular reference to the recognition of the role of the microbiologist, the infection control team and antibiotic policies are presented.

[Patient volume and facilities measurements as quality indicators of peri- and neonatal care: a review of data from the last 4 years]. / Volumen- und Ausstattungsmerkmale als peri- und neonatale Qualitätsindikatoren: Eine Ubersicht über Daten der letzten 4 Jahre.

AIM: This article reviews recent studies on the relationship between patient volume, level of care, and peri- or neonatal outcome for term and preterm infants. METHODS: A PubMed search was performed using various combinations of keywords related to neonates, patient volume and outcome published since 2000. RESULTS: Two studies on term infants showed that perinatal mortality in Norway and Germany was 2 - 3 times higher for term infants born in institutions with less than 500, and 40 - 80 % higher in those with < 1000 births/year compared to larger hospitals. For preterm infants, the mortality risk for those born in hospitals without a level III neonatal intensive care unit (NICU) was almost twice as high as for those born in hospitals with such an NICU. With regard to patient volume, studies from both the USA and Germany showed a significantly, up to 56 % higher mortality risk for infants admitted to units with less than 36 or 50 very low birth weight (VLBW) admissions per year compared to larger NICUs. CONCLUSIONS: Although patient volume or level of care are poor predictors of neonatal outcome, the above data provide arguments for a more rigorous perinatal centralisation, aiming to restrict term deliveries to hospitals with at least 1000 births per year and VLBW deliveries to perinatal centres with 24 h on-site availability of a neonatologist and at least 36 - 50 VLBW admissions per year. This may result in a significant reduction in perinatal mortality in Germany. In the interest of the families at risk of loosing their child, we must strive further to achieve this goal.

Limited comparability of classifications of levels of neonatal care in UK units. The ECSURF (Economic Evaluation of Surfactant) Collaborative Study Group.

AIM: To assess whether different classifications of neonatal care or dependency scales are comparable when used in multicentre studies of cost effectiveness. METHODS: A survey of classifications was used in a nationally representative group of 57 units in 1990-1, with a retrospective study of 10 354 cot days using patient records from a 5% random sample of 1042 admissions. Local and national classifications were correlated with medical and nursing procedures recorded for up to 26 days after each admission. RESULTS: Classifications varied substantially. Of the 57 units in our sample, 26 used one of two national classifications, sometimes modified; 17 used the Northern Neonatal Network dependency scale; and the other 14 did not record daily levels of care. In each classification, the highest level was having respiratory support by ventilation or continuous distending pressure through an endotracheal tube, nasal prongs, facemask or negative pressure device. This level of care was consistently comparable between classifications; lower levels were not. CONCLUSIONS: Retrospective comparisons between units with different classifications can only reliably differentiate between days with and without respiratory support. There is a pressing need to develop and validate more appropriate scales for prospective multicentre studies. These should relate activity to costs and outcome.

Future financial neonatal shock.

In a changing economic climate, the neonatologist must be aware of all of the forces that can affect the practice of neonatology. In addition to clinical issues, billing and reimbursement must take into account physician work and common procedural terminology (CPT) codes, which accurately describe the medical services and procedures delivered. An understanding of this coding and resource-based work unit system is necessary to prevent financial loss. The influence of managed care, capitation, fixed per-case reimbursement, practice guidelines and care maps have already seriously affected clinical practice patterns. The neonatologist must be proactive in negotiating contracts using historic information and outcome data to define and defend the quality of care provided.

Illness severity measured by CRIB score: a product of changes in perinatal care?

AIM: To determine the perinatal factors associated with initial illness severity (measured by the CRIB (clinical risk index for babies) score) and its relation to survival to discharge. METHODS: A retrospective study was made of intensive care nursing records on 380 inborn babies, of less than 31 weeks gestation or 1501 g birthweight, admitted to one unit between 1984-6 and 1991-4. RESULTS: Between the two time periods mean initial illness severity score increased significantly from 2.8 to 3.9. This was the result of an increase in the maximum appropriate inspired oxygen concentration in the first 12 hours. Risk adjusted survival did not improve over time after accounting for gestation but was significantly greater after accounting for CRIB score. Illness severity score was also significantly inversely associated with gestation and 1 and 5 minute Apgar scores, using multiple regression analysis. Between the two time periods there was also a 92% increase in the admission rate of babies under 31 weeks gestation, higher median 1 and 5 minute Apgar scores (6 vs 5 and 9 vs 8, respectively), more multiple births, and more caesarean section deliveries. CONCLUSIONS: The increase in illness severity score and admission rate may reflect changes in obstetric practice. The increase in illness severity score may also reflect changes in early neonatal care. However, after adjusting for CRIB score, risk adjusted mortality fell significantly, suggesting that neonatal care 12 hours from birth onwards had improved with time.

[Evaluation of a classification of newborns and maternity wards in the Loire-Atlantique department]. / Etude d'une classification des nouveau-nés et des maternités dans le département de Loire-Atlantique.

In order to assess the perinatal health policy in a French department in comparison with other policies, we performed a prospective transversal survey in the Loire-Atlantique for 5 weeks. Newborns were registered according to clinical data using the Paris pediatricians classification (classes 1 to 4) and maternity wards by number of health personnel and facilities using the American Academy of Pediatrician classification (I-III). 1316 newborns were registered. This survey showed that the health care organization in maternity wards is rational in the Loire-Atlantique for newborns in classes 1 and 4. However, care for newborns in classes 2 and 3 could be provided in maternity wards in classes II and III if available personnel and equipment is improved.

Evaluation of noise in the neonatal intensive care unit.

This study evaluated the noise level inside the incubators in a neonatal intensive care unit and identified its sources in order to attempt to reduce it. Although noise is not a proven risk factor as far as the sensory integrity of newborns is concerned, it is certainly an important cause of stress to them and a source of serious and dangerous changes in their behavioral and physiologic states. Noise recorded inside the incubators had two components. The first was background noise from the incubator motors, which varied from 74.2 to 79.9 dB, and was similar to environmental noise. The second source was impulsive events beyond 80 dB. These events were the result of voluntary and involuntary contact with the incubators' Plexiglas surface or to the abrupt opening and closing of their access ports. Considering its decibel levels and frequency, this latter component is undoubtedly an important source of stress to newborns. Moreover, these data reveal the need to train health care personnel on how to reduce such noise by taking more care in the handling of infants.

Cost efficiency of neonatal nurseries: the significance of unit size.

The cost of neonatal intensive care is high, and human and financial resources are finite. It is therefore essential to provide such care efficiently in terms of costs while still maintaining standards of care. We looked at the relationship of unit size to cost and determined the optimum and minimum size of the unit in terms of cost efficiency. Our data suggest that units with fewer than 6 ventilator cots were less cost-efficient than those with more cots while those with 12 ventilator cots were the most efficient. The calculations were done only up to 16 ventilator cots. Similarly, level II units were most cost-efficient when attached to an intensive care unit and had over 16 cots.

The problem of neonatal diagnosis related groups.

There is, as yet, no satisfactory set of Diagnosis Related Groups to measure the casemix and consumption of hospital resources in the care of newborn infants. To obtain further information, infants less than 28 days when admitted to the Royal Children's Hospital and Royal Women's Hospital, Melbourne were analysed. Both Refined Diagnosis Related Groups and Pediatric Modified Diagnosis Groups were used. Neonatal groups of the Pediatric Modified system included all infants aged less than 28 days on admission, whereas Refined Diagnosis Related Groups includes only those newborn infants who have diagnoses specific to the newborn period. Refined Diagnosis Related Groups and their higher order contained 1,237 discharges. Standard deviation and coefficient of variation and length of stay in these RDRG were high. However, if the patients in these RDRGs were further grouped according to PMDRGs, there appeared to be more homogeneous missing. The R2 values were four times higher. It is recommended that a satisfactory form of neonatal DRGs is to regroup patients in neonatal RDRGs through a PMDRG grouper.

The demand for neonatal intensive care.

In a one year prospective study within the Trent Regional Health Authority the demand for neonatal intensive care was estimated to be 1.1 cots per 1000 births. Intensive care level 1 (as defined by the British Paediatric Association and British Association for Perinatal Paediatrics) was determined by two separate techniques, which showed close agreement. Intensive care level 2 could not be measured directly, as the definition was too subjective. This aspect of demand was therefore estimated by using data derived from the treatment of babies transferred for intensive care. These findings represent a minimum estimate of need, as the data were obtained from a service constrained by having facilities well below the estimated level (roughly 60% of estimated demand). In the future other factors such as increased survival of extremely preterm infants will be likely to increase demand still further.

Efecto de algunos factores socioeconómicos y biologicos sobre el peso del recien nacido / Effect of some socioeconomic and biological factors on the weinght of the newborn

Las madres embarazadas, lactantes y niños pre-escolares, son los grupos más vulnerables a toda población, por ello actualmente y en forma creciente se ha venido prestando mayor atención a estos en lo que se refiere a la protección de su salud, lo que implica programas de inmunización en el caso de los niños y de educación en el campo de la nutrición y ciudados que se requieren durante el embarazo y la lactancia en el caso de la madre. La salud de la madre embarazada incide en el estado de salud del recien nacido, el ciudado de la misma implica la vigilancia médica durante toda la etapa del embarazo mediante consultasd prenatales periódicas en las que el control del peso corporal, enfermedades infecto contagiosas, alimentación etc. son medidas tendientes a proteger la salud del neonato...