Análisis de impacto presupuestario del implante intravítreo de dexametasona para el tratamiento del edema macular diabético / Budget impact analysis of dexamethasone intravitreal implant for the treatment of diabetic macular oedema

Objetivo: Determinar el impacto económico tras la inclusión del implante intravítreo de dexametasona para el tratamiento del edema macular diabético en un área sanitaria en España. Método: Se diseñó un modelo de impacto presupuestario a tres años para estimar los costes directos en pacientes adultos con edema macular diabético, desde la perspectiva del Sistema Nacional de Salud, considerando terapias intravítreas actualmente utilizadas (aflibercept/ ranibizumab/dexametasona). La población diana se obtuvo a partir de la prevalencia (6,41%) e incidencia (0,82%) del edema macular diabético publicadas para una población de 25.000 pacientes adultos. Se asumió un 20%, 30% y 40% anual de pacientes tratados con dexametasona, respectivamente. El coste total incluyó: coste farmacológico (precio de venta del laboratorio con deducción obligatoria y fraccionamiento de viales, según frecuencia de inyecciones necesarias cada año de tratamiento), administración intravítrea, seguimiento de pacientes y manejo de eventos oculares (cataratas, hipertensión ocular, endoftalmitis, hemorragia intravítrea y desprendimiento de retina) y cardiovasculares. El consumo de recursos según la práctica habitual fue estimado por expertos en retina y vítreo. Los costes unitarios (Euros 2016) se obtuvieron de la literatura y de bases de datos nacionales. Los análisis de sensibilidad evaluaron la robustez del modelo. Resultados: La inclusión del implante intravítreo de dexametasona supondría reducciones de 35.030 Euros (-4,2%), 10.743 Euros (-1,8%) y 5.051 Euros (-0,9%) cada año, respectivamente, disminuyendo principalmente por el menor número anual de inyecciones requeridas con dexametasona. La reducción anual promedio supondría 350 Euros, 96 Euros y 41 Euros por paciente

Objective: To assess the economic impact following the inclusion of an intravitreal implant of dexamethasone for the treatment of diabetic macular oedema in a healthcare area in Spain. Method: A 3-year budget impact model was designed to estimate healthcare direct costs for adult patients with diabetic macular oedema from the National Health System perspective. The approved therapies in use (aflibercept/ranibizumab/dexamethasone) were considered. The target population was estimated from published diabetic macular oedema prevalence (6.41%) and incidence (0.82%) for a population of 25,000 adults. Dexamethasone was assumed to be used annually in 20%, 30% and 40% of patients, respectively. Annual total costs included: drug acquisition (based on frequency of injections per every year, considering exfactory prices with mandatory deduction and split of vials), intravitreal administration, patient monitoring, management of cardiovascular and ocular adverse events (cataracts, increased intraocular pressure, endophthalmitis, vitreous haemorrhage and retinal detachment). Detailed resource consumption reflecting clinical practice was provided from local experts in retina and vitreous. Unitary costs (Euros 2016) were obtained from national databases and literature. Sensitivity analyses were performed to assess model robustness. Results: The inclusion of intravitreal dexamethasone implant would lead to annual cost savings of Euros 35,030 (-4.2%), Euros 10,743 (-1.8%) and Euros 5,051 (-0.9%), years 1-3 respectively. Total costs were reduced mainly by the fewer annual injections required by dexamethasone. The average annual incremental costs were - Euros 350, -Euros 96 and -Euros 41 per patient

Budget impact analysis of dexamethasone intravitreal implant for the treatment of diabetic macular oedema.

OBJECTIVE: To assess the economic impact following the inclusion of an intravitreal implant of dexamethasone for the treatment of diabetic macular oedema in a healthcare area in Spain. METHOD: A 3-year budget impact model was designed to estimate healthcare  direct costs for adult patients with diabetic macular oedema from the National  Health System perspective. The approved therapies in use  (aflibercept/ranibizumab/dexamethasone) were considered. The target  population was estimated from published diabetic macular oedema prevalence  (6.41%) and incidence (0.82%) for a population of 25,000 adults.  Dexamethasone was assumed to be used annually in 20%, 30% and 40% of  patients, respectively. Annual total costs included: drug acquisition (based on  frequency of injections per every year, considering exfactory prices with  mandatory deduction and split of vials), intravitreal administration, patient  monitoring, management of cardiovascular and ocular adverse events  (cataracts, increased intraocular pressure, endophthalmitis, vitreous  haemorrhage and retinal detachment). Detailed resource consumption reflecting  clinical practice was provided from local experts in retina and vitreous. Unitary  costs (€, 2016) were obtained from national databases and literature. Sensitivity  analyses were performed to assess model robustness. RESULTS: The inclusion of intravitreal dexamethasone implant would lead to  annual cost savings of €35,030 (-4.2%), €10,743 (-1.8%) and €5,051 (-0.9%), years 1-3 respectively. Total costs were reduced mainly by the fewer annual  injections required by dexamethasone. The average annual incremental costs  were -€350, -€96 and -€41 per patient. CONCLUSIONS: The inclusion of an intravitreal dexamethasone implant for the  treatment of diabetic macular oedema would lead to cost-savings for the  considered health area, mainly by reducing the administration costs.

Objetivo: Determinar el impacto económico tras la inclusión del implante intravítreo de dexametasona para el tratamiento del edema macular diabético en un área sanitaria en España.Método: Se diseñó un modelo de impacto presupuestario a tres años para  estimar los costes directos en pacientes adultos con edema macular diabético,  desde la perspectiva del Sistema Nacional de Salud, considerando terapias  intravítreas actualmente utilizadas (aflibercept/ranibizumab/dexametasona). La  población diana se obtuvo a partir de la prevalencia (6,41%) e incidencia  (0,82%) del edema macular diabético publicadas para una población de 25.000  pacientes adultos. Se asumió un 20%, 30% y 40% anual de pacientes tratados  con dexametasona, respectivamente. El coste total incluyó: coste farmacológico  (precio de venta del laboratorio con deducción obligatoria y fraccionamiento de  viales, según frecuencia de inyecciones necesarias cada año de tratamiento),  administración intravítrea, seguimiento de pacientes y manejo de eventos  oculares (cataratas, hipertensión ocular, endoftalmitis, hemorragia intravítrea y  desprendimiento de retina) y cardiovasculares. El consumo de recursos según la  práctica habitual fue estimado por expertos en retina y vítreo. Los costes  unitarios (€, 2016) se obtuvieron de la literatura y de bases de datos nacionales.  Los análisis de sensibilidad evaluaron la robustez del modelo. Resultados: La inclusión del implante intravítreo de dexametasona supondría reducciones de 35.030 € (­4,2%), 10.743 € (­1,8%) y 5.051 € (­ 0,9%) cada año, respectivamente, disminuyendo principalmente por el menor  número anual de inyecciones requeridas con dexametasona. La reducción anual  promedio supondría 350 €, 96 € y 41 € por paciente.Conclusiones: La inclusión del implante intravítreo de dexametasona para el  tratamiento del edema macular diabético supone ahorros para el área sanitaria  considerada, fundamentalmente por la reducción de costes de administración.

[Efficiency of the home intravenous antibiotics treatment in cystic fibrosis]. / Eficiencia del tratamiento antibiótico intravenoso domiciliario en la fibrosis quística.

BACKGROUND AND OBJECTIVE: The objective of our study was to determine the costs saving with the implementing of a home intravenous antibiotic treatment (HIVAT) program for patients with cystic fibrosis and to compare it with the conventional system (inpatient). PATIENTS AND METHOD: Consecutive patients in an adults cystic fibrosis unit were selected who received some days of HIVAT, between January 2002 and December 2004. For the analysis of costs saving of the HIVAT, we used the difference between the total costs of the avoided stay days and the costs generated by the domiciliary therapy (drugs, expendable equipment) and by the ambulatory medicine unit in case the patients were not hospitalized. All patients received a therapy with an intravenous antibiotic for a minimum of 14 days. All these data were provided by the accounting service of the hospital with the aid management Clinical Financier Program (GECLIF). RESULTS: 22 patients with cystic fibrosis needed 85 intravenous antibiotics treatments during the 3 years of the study, of which: 43 cycles were completely domiciliary, 14 inpatient and 28 were combined (hospital and home). The 71 cycles of HIVAT originated 909 days at home, with an average (standard deviation) of 12.80 (4.18) days and 43 treatments in ambulatory medicine unit. The home antibiotic treatments that originated greater cost (3,964.34 Euro) was meropenem (1 g/6 h) i.v. with linezolid (600 mg/12 h) via oral combination during 14 days, and in second place the association of ceftazidime, tobramycine and linezolid, whose cost in cycle of 14 days was of 2464.84 Euro. The average saving cost in the 3 years of study was of 2,647.29 Euro by each cycle of HIVAT and global 197,689.78 Euro. CONCLUSIONS: HIVAT obtained important sanitary costs saving and this was greater every year, not due to the increase of days at home, but due to the rising cost per day of hospital stays every new year.

Eficiencia del tratamiento antibiótico intravenoso domiciliario en la fibrosis quística / Efficiency of the home intravenous antibiotics treatment in cystic fibrosis

Fundamento y objetivo: El objetivo de nuestro trabajo ha sido estimar el ahorro de costes derivado de la implantación de un programa de tratamiento antibiótico intravenoso domiciliario (TAIVD), frente al esquema terapéutico tradicional (con ingreso hospitalario), en pacientes con fibrosis quística. Pacientes y método: Se incluyó consecutivamente en el estudio a los pacientes pertenecientes a una unidad de adultos de fibrosis quística que recibieron algún día TAIVD durante el período comprendido entre enero de 2002 y diciembre de 2004. Para el análisis de ahorro de costes del TAIVD se calculó la diferencia entre los costes de las estancias brutas evitadas y los generados por el tratamiento domiciliario (fármacos, material fungible) y en el hospital de día, en el caso de que el paciente no hubiese ingresado en el hospital. Todos los pacientes recibieron tratamiento antibiótico intravenoso un mínimo de 14 días. Los datos económicos fueron proporcionados por el Servicio de Contabilidad del hospital con la ayuda del programa de Gestión Clínico-Financiera (GECLIF). Resultados: Durante los 3 años del estudio 22 pacientes con fibrosis quística recibieron 85 ciclos de tratamiento antibiótico intravenoso; 43 fueron íntegramente domiciliarios; 14, hospitalarios y 28, mixtos (hospital y domicilio). Los 71 ciclos de TAIVD (incluidos los 28 mixtos) se desglosaron en 909 días en domicilio, con una media (desviación estándar) de 12,80 (4,18) días y 43 estancias en el hospital de día. Los tratamientos antibióticos que originaron mayor gasto en el domicilio (3.964,34 e) fueron la combinación de meropenem (1 g/6 h) intravenoso con linezolid (600 mg/12 h) por vía oral durante 14 días y, en segundo lugar, la asociación de ceftazidima, tobramicina y linezolid, cuyo gasto en un ciclo de 14 días fue de 2.464,84 e. El ahorro medio en los 3 años de estudio se estimó en 2.647,29 e por cada ciclo de TAIVD, y de forma global, en 197.689,78 e. Conclusiones: La implantación del programa de TAIVD supuso un importante ahorro de costes. Dicho ahorro fue mayor cada año, dado que el coste de la estancia hospitalaria se elevó de forma considerable cada año transcurrido

Background and objective: The objective of our study was to determine the costs saving with the implementing of a home intravenous antibiotic treatment (HIVAT) program for patients with cystic fibrosis and to compare it with the conventional system (inpatient). Patients and method: Consecutive patients in an adults cystic fibrosis unit were selected who received some days of HIVAT, between January 2002 and December 2004. For the analysis of costs saving of the HIVAT, we used the difference between the total costs of the avoided stay days and the costs generated by the domiciliary therapy (drugs, expendable equipment) and by the ambulatory medicine unit in case the patients were not hospitalized. All patients received a therapy with an intravenous antibiotic for a minimum of 14 days. All these data were provided by the accounting service of the hospital with the aid management Clinical Financier Program (GECLIF). Results: 22 patients with cystic fibrosis needed 85 intravenous antibiotics treatments during the 3 years of the study, of which: 43 cycles were completely domiciliary, 14 inpatient and 28 were combined (hospital and home). The 71 cycles of HIVAT originated 909 days at home, with an average (standard deviation) of 12.80 (4.18) days and 43 treatments in ambulatory medicine unit. The home antibiotic treatments that originated greater cost (3,964.34 e) was meropenem (1 g/6 h) i.v. with linezolid (600 mg/12 h) via oral combination during 14 days, and in second place the association of ceftazidime, tobramycine and linezolid, whose cost in cycle of 14 days was of 2464.84 e. The average saving cost in the 3 years of study was of 2,647.29 e by each cycle of HIVAT and global 197,689.78 e. Conclusions: HIVAT obtained important sanitary costs saving and this was greater every year, not due to the increase of days at home, but due to the rising cost per day of hospital stays every new year

Aminoimidazo[1,2-a]pyridines as a new structural class of cyclin-dependent kinase inhibitors. Part 1: Design, synthesis, and biological evaluation.

We have identified a novel structural class of protein serine/threonine kinase inhibitors comprised of an aminoimidazo[1,2-a]pyridine nucleus. Compounds from this family are shown to potently inhibit cyclin-dependent kinases by competing with ATP for binding to a catalytic subunit of the protein. Structure-based design approach was used to direct this chemical scaffold toward generating potent and selective CDK2 inhibitors. The discovery of this new class of ATP-site directed protein kinase inhibitors, aminoimidazo[1,2-a]pyridines, provides the basis of new medicinal chemistry tool in search for an effective treatment of cancer and other diseases that involve protein kinase signaling pathways.

Aryl[a]pyrrolo[3,4-c]carbazoles as selective cyclin D1-CDK4 inhibitors.

The synthesis of new analogues of Arcyriaflavin A in which one indole ring is replaced by an aryl or heteroaryl ring is described. These new series of aryl[a]pyrrolo[3,4-c]carbazoles were evaluated as inhibitors of Cyclin D1-CDK4. A potent and selective D1-CDK4 inhibitor, 7a (D1-CDK4 IC(50)=45 nM), has been identified. The potency, selectivity profile against other kinases, and structure-activity relationship (SAR) trends of this class of compounds are discussed.

Studies on cyclin-dependent kinase inhibitors: indolo-[2,3-a]pyrrolo[3,4-c]carbazoles versus bis-indolylmaleimides.

A series of indolo[2,3-a]pyrrolo[3,4-c]carbazoles and their bis-indolylmaleimides precursors have been prepared in order to compare their activity as D1-CDK4 inhibitors. Both enzymatic and antiproliferative assays have shown that the structurally more constrained indolo[2,3-a]pyrrolo[3,4-c]carbazoles are consistently more active (8-42-fold) in head-to-head comparison with their bis-indolylmaleimides counterparts. Cell-cycle analysis using flow cytometry have also shown that the indolocarbazoles are selective G1 blockers while the bis-indolylmaleimides arrest cells in the G2/M phase.

Synthesis of aryl- and heteroaryl[a]pyrrolo[3,4-c]carbazoles.

Synthesis of aryl- and hetero[a]pyrrolo[3,4-c]carbazoles by photochemical oxidation and Heck cyclization are described. Photochemical oxidation of 2-naphthyl indolyl maleimide affords two different carbazole regioisomers, depending on the reaction conditions. The regiochemistry of the cyclization can be controlled using the Heck reaction.

Imidazo[1,2-b]pyridazines, novel nucleus with potent and broad spectrum activity against human picornaviruses: design, synthesis, and biological evaluation.

A novel structural class of picornavirus inhibitors comprising an imidazo[1,2-b]pyridazine nucleus was discovered. 2-Aminoimidazo[1,2-b]pyridazines (6d, (E/Z)-7b, (E)-7d, (Z)-7d, (E/Z)-8b, (E)-10b, (E)-13a, (Z)-13a, (E)-13b, (Z)-13b, (E)-13c, and (Z)-13c) were designed and synthesized in an effort to identify potent broad spectrum antirhinoviral agents. A practical synthetic route to this chemical scaffold has been developed. The target compounds were evaluated in a plaque reduction assay and in a cytopathic effect assay. Our preliminary SAR studies highlight the minimum structural features required for antirhinovirus activity. Our data suggest that the nature of the linker between the phenyl and the imidazopyridazine moieties has a significant influence on the activity of these compounds. Oximes are slightly better than vinyl carboxamides at this position. The oximes are the most potent analogues against human rhinovirus 14 (HRV-14), and at the concentrations evaluated, no apparent cellular toxicity is noted. Furthermore, the E geometry appears to be a key element for activity; the Z isomer leads to a considerable loss in potency. Of particular interest, analogue 7b exhibits potent broad-spectrum antirhinoviral and antienteroviral activity when evaluated against a panel of seven additional rhino- and enteroviruses. The chemistry and the biological evaluations are discussed.

Novel, potent and selective cyclin D1/CDK4 inhibitors: indolo[6,7-a]pyrrolo[3,4-c]carbazoles.

The synthesis and CDK inhibitory properties of a series of indolo[6,7-a]pyrrolo[3,4-c]carbazoles is reported. In addition to their potent CDK activity, the compounds display antiproliferative activity against two human cancer cell lines. These inhibitors also effect strong G1 arrest in these cell lines and inhibit Rb phosphorylation at Ser780 consistent with inhibition of cyclin D1/CDK4.

3.1 Scholarship and the university.

Universities now exist in an environment of increasing accountability for their academic performance, both in teaching and research. Dental schools are expected to meet the academic expectations of their parent university and, in addition, to contribute to the health-care needs of the community. Individual staff members must achieve collectively the performance targets required of their school and individually must develop skills and expertise in their academic and clinical activities to merit tenure and promotion. This discussion examines the issues which impact on current problems of recruitment and retention of academic staff in dental schools internationally. The essential issue is career development in a manner which maintains the values that will ensure the credibility of dentistry as a scientifically based discipline and profession, while balancing the achievable academic needs with the added demands of achieving specialist clinical skills. Central to this balance is recognition that scholarship, which provides the bridge between research and teaching, can be broadly defined and that different individuals can be scholarly in a range of ways. Increasingly, schools are recognizing the importance of providing structured opportunities and guidance for career development of younger staff and of the need for flexibility in their criteria for tenure and promotion, recognizing that a diversity of individual strengths and teamworking are necessary both for the collective performance of the institution and the morale and development of the individual.

Evolución de la episiotomía: siguiendo dos tipos de cuidados / Evolution of an episiotomy: a follow up on two types of treatment

El cuidado unificado de la episiotomía es fundamental para prevenir las complicaciones que surgen en el puerperio. Se analiza mediante un estudio clínico comparativo en dos grupos de mujeres primíparas, la evolución de la episiotomía en función de la aplicación de povidona yodada al 0,4 por ciento a través de ocho variables cualitativas analizadas de forma independiente. Por su mayor influencia en la evolución de la episiotomía se ha evaluado en profundidad una de las variables que definen su calidad: la dehiscencia. Del estudio se concluye que el fomento del autocuidado influye en una mejor evolución de la episiotomía con respecto a la aplicación del antiséptico (AU)

Comparison of different methodological approaches to identify risk factors of nosocomial infection in intensive care units.

OBJECTIVE: Comparison of statistical methods and measurement scales to identify nosocomial infection risk factors in intensive care units (ICU). DESIGN: Prospective study in 558 patients admitted to the ICU of a referral hospital between February and November 1994. METHODS: Analysis using three logistic regression models, three standard Cox regression models, and two Cox regression models with time-dependent extrinsic factors. Different scales were used to measure exposures to risk factors (dichotomous, ordinal, quantitative, and time-dependent variables). RESULTS: The most appropriate models were those that measured exposure using dichotomous variables. Models using ordinal or quantitative variables estimated biased coefficients and/or failed to comply with the statistical assumptions underlying the analyses. The Cox regression model with quantitative time-dependent variables met all the statistical assumptions, obtained a precise assessment of risk by exposure time, and estimated unbiased coefficients. CONCLUSIONS: The Cox regression analysis with quantitative time-dependent variables is the most valid alternative for assessing the risk of nosocomial infection per day of exposure to an extrinsic risk factor in the ICU.

Nosocomial infection in an intensive-care unit: identification of risk factors.

OBJECTIVE: To identify risk factors predictive of nosocomial infection in an intensive-care unit (ICU) and to identify patients with a higher risk of nosocomial infection using a predictive model of nosocomial infection in our ICU. DESIGN: Prospective study; daily concurrent surveillance of intensive-care-unit patients. SETTING/PATIENTS: All patients admitted for at least 24 hours to the ICU of a tertiary-level hospital from February to November 1994 were followed daily. METHODS: Variables measuring extrinsic and intrinsic risk factors for nosocomial infection were collected on each patient during their ICU stay, and the Cox Proportional Hazards multivariable technique was used to identify the variables significantly associated with infection. RESULTS: The population studied consisted of 944 patients. The main risk factors identified were intrinsic; the significant extrinsic risk factors identified were head of the bed in a horizontal (< 30 degrees) position (this variable presented the highest increase of the infection hazard ratio) and the use of sedative medication. Patients presenting the highest risk scores using the predictive model are those with the highest risk of nosocomial infection. CONCLUSIONS: The important preventive measures derived from our results are that underlying conditions suffered by the patient at the ICU admission should be corrected promptly, the depression of the patient's level of consciousness with sedatives should be monitored carefully, and the horizontal position of the head of the bed should be avoided totally. Patients with a high risk of infection can be the target of special preventive measures.