[Access to orphan drugs for the treatment of spinal muscular atrophy in Spain]. / Acceso a medicamentos huérfanos para el tratamiento de la atrofia muscular espinal en España.

INTRODUCTION: Spinal muscular atrophy (SMA) is a rare disease whose diagnosis and treatment are complex. In Spain, there are two orphan medicines that are currently financed by the state, nusinersen and onasemnogene abeparvovec and, a third in process, risdiplam. The objective was to detect possible causes of inequity in the diagnosis and treatment of SMA in Spain. MATERIALS AND METHOD: Descriptive study realized in two phases: a first phase of bibliographic revision and a second phase of semi-structured interviews with clinical experts in SMA in Andalusia, Castilla-La Mancha, Catalonia and Murcia. RESULTS: The number of centers, services or units of reference, the availability of regional autonomous plans for rare diseases and pilot programs of neonatal screenings can regulate access to treatments. The number of new patients diagnosed per year is estimated between one and six in the four autonomous communities (ACs) of Spain studied. Differences were not found in logistical resources. Two of the four ACs studied have regional autonomous plans for rare diseases, however, their utility has only had relevance in one of two of the ACs. CONCLUSIONS: Important differences in access to nusinersen were not identified in the studied ACs The diagnosis of SMA requires clinical specialized experts and specialized centers for early intervention of disease-modifying therapies.

TITLE: Acceso a medicamentos huérfanos para el tratamiento de la atrofia muscular espinal en España.Introducción. La atrofia muscular espinal (AME) es una enfermedad rara cuyo diagnóstico y tratamiento es complejo. En España hay dos medicamentos huérfanos financiados por el Sistema Nacional de Salud, nusinersén y onasemnogén abeparvovec, y un tercero, risdiplam, pendiente. El objetivo fue analizar el acceso a los fármacos modificadores de la AME y detectar posibles causas de inequidad. Materiales y método. Estudio descriptivo realizado en dos fases: revisión bibliográfica y entrevistas semiestructuradas a expertos clínicos en AME de las comunidades autónomas (CC. AA.) de Andalucía, Castilla-La Mancha, Cataluña y Murcia. Resultados. El número de centros, servicios o unidades de referencia, la disponibilidad de planes autonómicos para enfermedades raras y los programas piloto de cribado neonatal pueden modular el acceso a los nuevos tratamientos farmacológicos. El número de nuevos pacientes diagnosticados al año se estimó entre uno y seis en cada una de las CC. AA. estudiadas. Dos de las cuatro CC. AA. estaban participando en ensayos clínicos. El tiempo desde la prescripción a la administración de nusinersén estaba entre siete y 60 días. Sólo Cataluña comunicó experiencia con onasemnogén abeparvovec a 30 de junio de 2022. Dos CC. AA. de las cuatro estudiadas disponen de plan autonómico para enfermedades raras; no obstante, se identificó como relevante para el tratamiento de la AME sólo en una de ellas. Conclusiones. No se identificaron diferencias importantes en el acceso al nusinersén en las CC. AA. estudiadas. El diagnóstico de la AME requiere personal clínico experto y centros especializados para iniciar precozmente los tratamientos modificadores de la enfermedad.

Remote pharmaceutical care for patients with rheumatoid arthritis and psoriasis.

BackgroundAccess to drugs with hospital-restricted dispensation, such as those for patients with rheumatoid arthritis or psoriasis, is regulated by healthcare policy. These drugs have the greatest cost-effective impact on the healthcare system. This is why a model for Pharmaceutical Care based on follow-up teleconsultations was defined in our hospital to improve patient well-being. Objective To evaluate clinical changes on patients when our remote Pharmaceutical Care model is applied and describe the work carried out by pharmacists when applying it. Setting Pharmacy Department of a Hospital in Barcelona, Spain. Method Cross-sectional observational study of the remote Pharmaceutical Care model developed by Clinical Pharmacists. All patients diagnosed with psoriasis or rheumatoid arthritis who were receiving active treatment with Hospital/Specialist only drugs, during the period from May to December 2018, were included. Main outcome measures The corresponding healthcare activity was recorded and to determine the utility of the model, the clinical response to treatment of patients included in the study was recorded. Results The implementation of teleconsultation is statistically related to the biological treatment response of patients with psoriasis (p = 0.006) and rheumatoid arthritis (p = 0.019). In those patients the healthcare activity of calculating and/or recording clinical variables of effectiveness/safety is statistically associated to biological treatment response (65.62% vs 35%, p = 0.015 and 73.14% vs 53.26%, p = 0.003). Conclusions The implementation of the model described lends added value to traditional pharmacotherapeutic management of biological treatments in patients with rheumatoid arthritis and psoriasis since response is improved but patient well-being is not diminished.

[Dose intensity received in breast cancer treatment with chemotherapy]. / Intensidad de dosis recibida en el tratamiento quimioterápico del cáncer de mama.

OBJECTIVE: To know relative dose intensity (RDI) in patients with breast cancer treated with chemotherapy. To determine the number of patients where RDI was < 85% of that programmed and the possible cause. METHOD: Retrospective study, four-month selection period. The following were recorded: age, body surface, protocol applied, intention of treatment, frequency of administration of cycles, number of cytostatic treatments previously received and filgrastim administration. The average RDI per patient and protocol was calculated. RESULTS: 110 patients were analysed, the average age of them being 55.4 years (interval: 31-84), average body surface 1.7 m2 (1.3-2.4). Overall average RDI was 91.0% (SD 10.7). 93.8% (10.6), 95.8% (6.3) and 81.9% (18.5) in neoadjuvant, adjuvant and palliative treatments, respectively. 20% of the patients did not reach a RDI = 85% of that programmed, average RDI 69.5% (3.29). A delay in the administration of chemotherapy equal or greater than seven days occurred in 45.4% of the cases, average RDI 80.7% (16.0). In the episodes where the dose was reduced because of toxicity, the RDI was 75.6% (13.6). Significant inverse ratios were obtained with age (p = 0.02) and line of treatment (p = 0.03) with the RDI. In 36.8%, dose reduction was caused by neutropenia; 52.9% received filgrastim. CONCLUSIONS: Most patients received the appropriate RDI. Age, previous treatments and intention of treatment were the variables with the greatest impact on the dose received. The delay in administering the cycle was the most frequent act minimising the toxicity and which least affected the treatment.

Pharmacokinetics and tissue residues of an oxytetracycline/diclofenac combination in cattle.

Eight male cattle were given a combined dose containing 20 mg/kg oxytetracycline and 0.5 mg/kg diclofenac intramuscularly. Blood samples were drawn at different times until 168 h after administration. Two experimental animals were slaughtered by humane means at weekly intervals up to 28 days after administration. Samples of muscle, injection zone tissue, liver, kidney and fat were obtained. Oxytetracycline and diclofenac concentrations were determined by high performance liquid chromatography. Kinetic analysis was performed by linear regression using the CSTRIP programme. Plasma oxytetracycline concentration showed a maximum (Cmax) of 3.89 +/- 1.48 microg/ml and a prolonged elimination half-life (T1/2beta: 47.73 +/- 18.33 h). The diclofenac plasma profile showed high Cmax (577.62 +/- 238.40 ng/ml), and its T1/2beta was also prolonged (30.48 +/- 9.42 h). Oxytetracycline concentrations were measurable in liver and adipose tissue until day 21 after administration, but all tissue samples were negative for diclofenac at 21 days. The long elimination half-life of diclofenac was an unexpected finding; its T1/2beta in humans is 1.1 h.

[Budget impact analysis of the treatment of chronic hepatitis C in a hospital]. / Análisis de impacto presupuestario en el tratamiento de la hepatitis por virus C en un hospital.

OBJECTIVE: To perform a budget impact analysis (BIA) of the treatment with pegylated interferon (pegIFN), alfa-2a or alfa-2b, plus ribavirin in patients with chronic hepatitis C (CHC). METHOD: An interactive model has been designed from the inputs obtained from hospital databases. Prices for pegIFN and RIB have been taken from the hospitals considering their respective discounts. Only pharmacological costs (euros 2005 values) for the options have been considered. Both strategies have been considered as therapeutic equivalents. RESULTS: The number of patients with CHC evaluated in the model has been of 117, with an average age of 42 years and an average weight of 75 kg. The genotypes of the patients were: G1/4, 85% and; G2/3, 15%. Discontinuation of the treatment at week 12 took place in 26% of the patients. The average duration of treatment has been of 37 weeks. Total cost of the 117 evaluated patients ranged between 942,632-952,109 and 861,646-880,751 euros for the treatment with pegIFN alfa-2a + RIB and pegIFN alfa-2b + RIB, respectively. CONCLUSIONS: BIA models can be useful for the inclusion or reassessment of drugs in formularies. In this case, the treatment with pegIFN alfa-2b + RIB (in comparison with pegIFN alfa-2a + RIB) is an efficient strategy although it depends on acquisition prices, and so, it would be rarely useful in other centres. In our hospital it would produce a budgetary saving that would range from 71,358 to 80,986 euros, which would represent a 7.5-8.6% of the total cost of the pharmacological treatment of the CHC.

[How to increase the involvement of casualty patients in their treatments: efficacy of some informative posters]. / Cómo aumentar la implicación del paciente de urgencias en su tratamiento? Eficacia de unos pósters informativos.

OBJECTIVE: To determine whether posters/leaflets increase doctors' information on the allergies and on the medication their patients are taking and patients' understanding of their treatment. DESIGN: First stage: multi-centre transversal descriptive study. Second stage: intervention with control and without randomisation. SETTING: Primary care medical emergency services (MES). PARTICIPANTS: MES patients under prescribed drug treatment. INTERVENTIONS: Use of posters/leaflets. MAIN MEASUREMENTS: 1) Proportion of patients for whom the doctor was ignorant of allergies to drugs or of accompanying medication. 2) Proportion of prescriptions in which patients understood the dosage of the medication prescribed. SOURCE: ad hoc questionnaire to patients. ANALYSIS: chi2 test (category variables). In some cases, the Breslow-Day and Tarone tests were conducted. RESULTS: Total patients included, 1233; 1766 prescriptions analysed; 53.4% women. Mean age: 29+/-18 years old. 1) Doctor's understanding of accompanying medication: at the second stage, drop of 25.5% (95% CI, 33.5-17.5) for intervention group versus drop of 12.5% (95% CI, 19.8-5.2) for control group, in the number of patients for whom the doctor did not know the medication (P=.024). 2) Patient's understanding of dosage: at the second stage, increase of 16.8% (95% CI, 9.8-23.8) for intervention group, versus a decrease of 1% in control group, in the medicines whose dosage the patient was aware of (P<.001). CONCLUSIONS: The dissemination of posters/leaflets was effective in increasing patients' knowledge of their medication's dosage and doctors' understanding of questions affecting prescription.

[Nutrient absorption rate from the peritoneal cavity in rats]. / Velocidad de absorción de nutrientes desde la cavidad peritoneal de ratas.

A study has been done of the absorption/elimination kinetics of nutritive substances such as glucose, amino acids and fats from the peritoneal cavity. For this purpose, 48 male Wistar rats were administered an intravenous or intraperitoneal "bolus" of 2 microCi of L-glucose-C14/250 g of body weight, 3 microCi of D-alanine-L-C14/250 g and 0.4 g of Intralipid/250 g body weight. A two-compartment pharmacokinetic model was applied to determine the absorption, elimination and distribution constants among the different body compartments of each of these substrates, as well as the absorption and elimination halflife. When the areas under the curves were compared following intravenous and intraperitoneal infusion, the total physiological availability or fraction of dose absorbed over a given period of time were calculated. A higher absorption and elimination constant for glucose and amino acids as compared to fats was found. Higher than 90% absorption for all substrates was found, but since in the case of fats the elimination constant is lower and longer the elimination halflife, we must be cautious regarding its infusion rate.

Improved survival in intestinal ischemia by allopurinol not related to xanthine-oxidase inhibition.

Allopurinol, a xanthine-oxidase (XO) inhibitor, has been used to improve the resistance to ischemia with disappointing results that have been attributed to administration regimen of the drug. Our aim was to investigate the effect of different administration schedules of allopurinol on the survival in rats undergoing intestinal ischemia testing the blockade of XO. Intestinal ischemia was achieved by 90 min of clamping the superior mesenteric artery (SMA) close to its origin from the aorta. Three groups of animals were evaluated: A-group: only the allopurinol solvent was given; B-group: the full dose of allopurinol (100 mg/k b.w.) was given iv and C-group: the 75% dose was administered orally 24 hr before and the remaining 25% was administered 30 min before. Survival was evaluated at 48 hr and the blockade of XO was assayed by High Efficacy Liquid Chromatography (HELC) in homogenate of intestinal wall. Survival was only improved in the C-group (P = 0.02). Levels of hypoxanthine were significantly increased both in B-group and C-group (P = 0.003) when compared with the A-group. Levels of uric acid in B-group (P = 0.0003) and C-group (P = 0.0009) were significantly decreased with respect to A-group. That means that an effective blockade of XO is achieved whichever the regimen of administration. Allopurinol and oxypurinol levels were significantly increased (P = 0.05 and P = 0.008) in C-group when compared with B-group. We conclude that the protective effect of allopurinol on survival in intestinal ischemia in rats is not related to the blockade of XO but rather to the allopurinol and oxypurinol levels in intestinal wall.

[Effect of xanthine oxidase inhibitors on the prognosis of acute intestinal ischemia]. / Efecto de los inhibidores de la xantino-oxidasa sobre el pronóstico de la isquemia intestinal aguda.

During the last few years, the scientific field has focused its attention on the pathogenic role of free radicals in the process of ischemia-revascularization. It is a well-known fact that xanthine oxidase is an important source of tissular free radicals. Bearing this in mind, we designed an experimental protocol to analyse the effect of allopurinol (a xanthine oxidase inhibitor) in the survival of rats after the occlusion of the superior mesenteric artery during a period of 90 minutes and its action on the superoxide radical liberation. The concentration of oxipurinol and allopurinol in the ischemic area (intestine), liver and blood were measured. We concluded that the administration of allopurinol increased the survival rate, which is correlated to higher concentrations of allopurinol and oxipurinol in the inner part of the intestinal cells. A correlation between the survival rate and superoxide radicals was not found.

Urinary excretion kinetics of p-nitrophenol following oral administration of parathion in the rabbit.

The urinary excretion kinetics of p-nitrophenol were studied in rabbits following oral administration of parathion at a dose of 3 mg/kg. Elimination of p-nitrophenol began rapidly, and of the total amount excreted during the study period, 46% was excreted in the first 3 h; 85% was excreted at 6 h after administration of the pesticide. The mean maximum excretion rate of p-nitrophenol was 111.15 +/- 61.02 micrograms/h reached in a time of 0.77 +/- 0.26 h. The formation and disappearance rate constants of the metabolite were 2.85 +/- 2.80 h-1 and 0.80 +/- 0.28 h-1, respectively. A linear relationship was observed between the plasma concentrations of parathion and the urinary excretion rate of p-nitrophenol.

Toxicokinetics of parathion in the rabbit.

The plasma kinetics of parathion were studied in rabbits after i.v. administration of a dose of 1.5 mg/kg and oral administration of 3 mg/kg. The time course of parathion plasma levels administered intravenously followed a three-compartment kinetic model statistically, whereas when administration was oral, the optimum kinetic model proved to be two-compartmental. The process of the absorption of parathion is very fast with a mean value for the absorption constant (ka) of 33 +/- 15.41 h-1. The slow disposition half-lives for i.v. and oral administration had mean values of 5.08 +/- 3.08 and 1.08 +/- 0.27 h, respectively. From the values established for the parameters defining the distribution process the wide accessibility of parathion to the different body organs and tissues may be seen. Although the compound has a high elimination constant, this process is not limiting to distribution.

Peri-incisional and preoperative administration of cefmetazole for the prophylaxis of wound infection after appendicectomy.

The tissue and blood levels of Cefmetazole are compared after preoperative administration of a single dose of 30 mg/K body weight of the antibiotic administered intravenously (15 patients) and peri-incisionally (30 patients) to patients scheduled for emergency appendicectomy. Local and general tolerance to the antibiotic was good by both routes. No local or general complications arose in any of the patients. As expected, the tissue concentrations achieved with peri-incisional infiltration were significantly higher than those obtained by the intravenous route. With the blood levels, exactly the opposite happens at the start of the operation whereas at the end, there were no significant differences between the two routes employed. The prophylactic administration by peri-incisional infiltration is an easy and safe method which provides high tissue concentrations simultaneously with adequate blood levels and should be considered as useful in the preoperative administration of antibiotics for prophylaxis.