Relationship between Medication-Related Osteonecrosis of the Jaw and CDK4/6 Inhibitors in Breast Cancer.

OBJECTIVE: We aimed to evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. METHODS: This was a multicentre, retrospective, observational study. All patients with breast cancer treated with denosumab (January 2011-December 2022) were included. The relationship between CDK4/6 inhibitors and MRONJ was analysed. RESULTS: A total of 243 patients were included, ninety-five (44.2%) of whom used a CDK4/6 inhibitor. There were 21 patients with MRONJ. In patients treated with denosumab without CDK4/6 inhibitors, the incidence of MRONJ and mean time to the occurrence of MRONJ were 6.6% (8/120) and 16.8 months (SD 7.8), respectively; in patients treated with denosumab and CDK4/6 inhibitor, these values were 13.7% (13/95) and 15.4 months (SD 8.7), respectively. The difference in the incidence was not significant (p = 0.085). Among the 19 patients who used abemaciclib, the probability of MRONJ occurrence was significantly higher compared to patients not using CDK4/6 inhibitors (p = 0.0178). CONCLUSIONS: These results suggest that the incidence of MRONJ in patients with metastatic breast cancer treated with denosumab is higher, and the onset of MRONJ occurs earlier in the presence of CDK4/6 inhibitors. The differences were statistically significant in the patients who used abemaciclib. Given that the use of this combination is very common in routine clinical practice, it would be advisable to carry out larger prospective studies to clarify the risk of this association.

Effectiveness of the Combined Use of a Brain-Machine Interface System and Virtual Reality as a Therapeutic Approach in Patients with Spinal Cord Injury: A Systematic Review.

Spinal cord injury has a major impact on both the individual and society. This damage can cause permanent loss of sensorimotor functions, leading to structural and functional changes in somatotopic regions of the spinal cord. The combined use of a brain-machine interface and virtual reality offers a therapeutic alternative to be considered in the treatment of this pathology. This systematic review aimed to evaluate the effectiveness of the combined use of virtual reality and the brain-machine interface in the treatment of spinal cord injuries. A search was performed in PubMed, Web of Science, PEDro, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, and Medline, including articles published from the beginning of each database until January 2023. Articles were selected based on strict inclusion and exclusion criteria. The Cochrane Collaboration's tool was used to assess the risk of bias and the PEDro scale and SCIRE systems were used to evaluate the methodological quality of the studies. Eleven articles were selected from a total of eighty-two. Statistically significant changes were found in the upper limb, involving improvements in shoulder and upper arm mobility, and weaker muscles were strengthened. In conclusion, most of the articles analyzed used the electroencephalogram as a measurement instrument for the assessment of various parameters, and most studies have shown improvements. Nonetheless, further research is needed with a larger sample size and long-term follow-up to establish conclusive results regarding the effect size of these interventions.

The effects of obesity on longitudinal ventricular and atrial strain in a rural population of Spanish children and adolescents, evaluated by a new strain software.

BACKGROUND AND OBJECTIVES: Research on the relationship between body mass index (BMI) and strain values in children and adolescents is limited. Our aim was to analyse the relationship between BMI and strain values of both ventricles and left atrium in children and adolescents. METHODS: Both ventricles and left atrial strain values were compared among different BMI categories in children and adolescents from a town in the South of Spain. RESULTS: Of the 198 subjects, aged 6-17 years, 53% were of normal weight, 26% were overweight and 21% had obesity. Lower absolute values of left ventricular global longitudinal strain (25.9 ± 2.0% vs. 26.9 ± 2.2%, p = 0.002) and right ventricular free wall longitudinal strain (29.5 ± 4.2% vs. 30.8 ± 4.5%, p = 0.04) were found in subjects with obesity and overweight versus subjects with normal weight. A lower right ventricular four-chamber longitudinal strain was also observed in males with obesity and overweight (24.8 ± 3.3% vs. 26.4 ± 3.6%, p = 0.03). Statistically significant negative correlations of BMI were found for all ventricular, but not atrial, strain values in univariate analysis. This association turned non-significant for right ventricular four-chamber longitudinal strain in multivariate analysis. CONCLUSIONS: Utilizing this new strain software, children and adolescents with high BMI were associated with significantly lower values for left and right ventricular free wall longitudinal strain, without impact in left atrial strain.

Analysis of neutropenia as a predictive factor of the efficacy of trifluridine-tipiracil treatment.

OBJECTIVES: Trifluridine-tipiracil (TAS-102), an oral cytotoxic agent used in adult patients with refractory metastatic colorectal cancer (mCRC), has been associated with neutropenia (chemotherapy-induced neutropenia) (CIN)). MATERIALS AND METHODS: We evaluated the efficacy and safety of TAS-102 in a group of 45 mCRC patients (median age 66 years) in Huelva province, Spain, in a retrospective, multicenter observational study. RESULTS: We showed that the association between TAS-102 and CIN can be used as a predictor of efficacy. 20% (9/45) of patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 had received at least one previous chemotherapy treatment. Overall, 75.5% (34/45) and 28.9% (13/45) had received anti-VEGF and anti-EGFR monoclonal antibodies, respectively. Additionally, 80% (36/45) of patients had received third-line treatment. The mean treatment period, duration of overall survival (OS), and duration of progression-free survival (PFS) were 3.4, 12, and 4 months, respectively. A partial response was seen in 2 patients (4.3%), and disease stabilization was observed in 10 patients (21.3%). Neutropenia was the most frequent grade 3 - 4 toxicity (46.7%; 21/45). Other findings were anemia (77.8%; 35/45), all grades of neutropenia (73.3%; 33/45), and gastrointestinal toxicity (53.3%; 24/45). The dose of TAS-102 needed to be reduced in 68.9% (31/45) of patients, whereas treatment needed to be interrupted in 80% (36/45) of patients. Grade 3 - 4 neutropenia was a positive prognostic factor for OS (p = 0.023). CONCLUSION: A retrospective evaluation shows that grade 3 - 4 neutropenia is an independent predictor of treatment response and survival in patients undergoing routine treatment for mCRC, but this finding needs confirmation in a prospective study.

Results of the Protocolization of a Telepharmacy Program: Patient Selection and Dispensation Interruption Criteria.

Objective: To analyze the impact of applying criteria for patient selection and interruption of dispensation in a telepharmacy program. Secondary objective: to conduct a socioeconomic analysis of requests for telepharmacy after applying the criteria. Methods: A retrospective observational study was conducted. We applied the criteria from September 1, 2021 to December 31, 2021 and reviewed the impact of their application by comparing the prior period (October 14, 2020-August 31, 2021) with the period when the criteria were applied. We analyzed the evolution of applications over time, the number of users, the evolution over time of rejected applications, and the associated reasons. Finally, we studied how the average income and distance to hospital are related to the number of requests. This study was reviewed by the authors' institutional ethics committee and was considered exempted from further review. Results: We applied the criteria to 2,379 patients. Dispensations by telepharmacy increased progressively. We provided telepharmacy services to 41.7% of all outpatients and rejected 962 applications (65% after the criteria were applied). The main pre- and postcriteria reasons for rejecting applications were refusal without express reason and the patient having sufficient medication, respectively. All patients corrected the situation that caused rejection. Telepharmacy requests and distance to hospital were not related, although the number of requests and average income were related. Conclusions: We provided pharmaceutical care with this protocol and encouraged patients to correct the reasons for interrupted dispensations. The new criteria render telepharmacy available to all patients, regardless of where they live or their purchasing power. Lower-income individuals use telepharmacy more often.

The Assessment of Myocardial Longitudinal Strain in a Paediatric Spanish Population Using a New Software Analysis.

BACKGROUND: Two-dimensional speckle-tracking echocardiography (2DSTE) has been present for years. However, it is underutilized due to the expertise and time requirements for its analysis. Our aims were to provide strain values in a paediatric Spanish population and to assess the feasibility and reproducibility of a new strain software analysis in our environment. METHODS: A cross-sectional study of 156 healthy children aged 6 to 17 years. Longitudinal strain (LS) analysis of the left ventricle, right ventricle, and left atrium was performed. Feasibility and reproducibility were assessed. The associations of clinical and echocardiographic variables with strain values were investigated by multivariate analysis. RESULTS: Mean age was 11 ± 3 years (50% female). Feasibility of LS measurement ranged from 94.2% for left ventricle global LS (LVGLS) to 98.1% for other chamber strain parameters. Strain values were 26.7 ± 2.3% for LVGLS; 30.5 ± 4.4% and 26.9 ± 4% for right ventricle free wall LS (RVFWLS) and four chambers view LS (RV4CLS) respectively; and 57.8 ± 10.5%, 44.9 ± 9.5%, and 12.9 ± 5.5% for left atrium LS reservoir phase (LALSr), conduct phase (LALScd) and contraction phase (LALSct), also respectively. Body surface area (BSA) and age presented a negative correlation with strain values. Higher values were found in females than in males, except for LALScd. Excellent intra- and inter-observer reproducibility were found for right and left ventricular strain measurement, with intraclass correlation coefficients (ICC) ranging from 0.88 to 0.98, respectively. In conclusion, we described strain values in a healthy Spanish paediatric population. LS assessment by this new strain analysis software by semi-automatic manner was highly feasible and reproducible.

Inotersen and severe thrombocytopenia: 2 case reports and review.

Hereditary transthyretin amyloidosis (hATTR) is an ultra-rare illness. Inotersen is a 2'-O-methoxyethyl (2'MOE)-modified antisense oligonucleotides (ASO) approved in 2018 as a polyneuropathy treatment for adults with hereditary transthyretin amyloidosis stages 1 or 2. Inotersen can produce grade 4 thrombocytopenia as a severe adverse reaction that can lead to potentially fatal hemorrhage complications. We describe our experience in the management of severe thrombocytopenia with inotersen. The onset of the thrombocytopenia and the incidences described in the cases in our hospital are different from that described in the literature. Also, recovery of platelet levels was faster in our patient who was administered human immunoglobulin G, which suggests that there is an immunological component.

Role of obesity and blood pressure in epicardial adipose tissue thickness in children.

BACKGROUND: Elevated body mass index (BMI) has been associated with cardiac changes, such as higher epicardial adipose tissue (EAT) thickness. This fat has been identified as a predictive factor of cardiovascular diseases during adulthood. However, few studies have tested the association of multiple cardiovascular risk factors (high weight or blood pressure) with EAT in adolescents and children. Therefore, the main objective of this current research was to determine the impact of BMI, overweight, obesity, and blood pressure on EAT thickness in children. METHODS: A descriptive cross-sectional study focused on elementary and high school students aged 6-16 years was carried out by utilizing diverse measurements and instruments, such as echocardiography. RESULTS: EAT thickness (N = 228) was linked to sex (more predominant in boys 2.3 ± 0.6; p = 0.044), obesity (2.3 ± 0.6; p < 0.001), and hypertension (2.6 ± 0.6; p = 0.036). The logistic regression indicated that age, sex, and BMI seemed to be more relevant factors in EAT thickness in children (adjusted R square = 0.22; p < 0.001). CONCLUSIONS: This paper examined the associations of sex, age, and cardiovascular risk factors (arthrometric measures and blood pressure) with EAT thickness, indicating that it is necessary to assess whether the findings are associated with future events. IMPACT: Excessive weight gain and blood pressure in the early stages of life have been associated with adipose tissue. This increase in weight and blood pressure has been attributed to alterations in the epicardial adipose tissue linked to anthropometric markers in adults, but no related study has been implemented in Spanish children. This study revealed how higher epicardial adipose tissue is linked to body mass index, other anthropometric parameters, and blood pressure in Spanish children. These measurements are related to high epicardial adipose tissue thickness, which in early stages does not imply pathology but increases the risk of developing cardiovascular diseases.

Relationship between overweight and obesity and cardiac dimensions and function in a paediatric population.

Obesity in adults is associated with left ventricular hypertrophy, dilatation, and myocardial fibrosis, as well as heart failure and coronary heart disease. These associations have been studied to a lesser extent in the paediatric population. This study aims to investigate the relationship between obesity and cardiac structure and function in the paediatric population. In a southern Spanish village, we selected all inhabitants aged 6-17 years stratifying by age, gender, and educational centres. We performed a complete transthoracic echocardiogram evaluating all the cardiac morphological and functional parameters commonly measured in an echocardiographic study. There were 212 children and adolescents included. Of them, 48.1% were males. The mean age was 10.9 ± 3.0 years. A total of 106 (50%) were normal weight, 57 (26.9%) overweight, and 49 (23.1%) obese. Sex and age were similar in all three groups. Overweight and obesity were associated with larger left ventricular end-diastolic and end-systolic volumes (p < 0.0005), greater left ventricular mass (p < 0.0005), and smaller ejection fraction (p < 0.0005). They were also associated with larger atrial, aortic, and right ventricular size. Lateral and mean E/e' ratios were higher (p = 0.007 and p = 0.01 respectively). Body mass index was independently associated with all cavity size variables as well as left ventricular ejection fraction. CONCLUSION: Childhood obesity is independently associated with larger heart chambers, greater left ventricle mass, and smaller left ventricle ejection fraction. WHAT IS KNOWN: • Childhood obesity is related to the development of cardiovascular risk factors and is considered an epidemic of the twenty-first century; its prevalence is rising. WHAT IS NEW: • Childhood overweight and obesity lead to changes in cardiac structure and function which, although not considered clinically pathological, are significant and a result of obesity, and which behave as unfavourable incipient alterations at an early age.

Adaptación transcultural a la versión española del cuestionario “Structured History of Medication Use” para la conciliación de la medicación al ingreso / Cross-cultural adaptation to the Spanish version of the “Structured HIstory of Medication Use” questionnaire for medication reconciliation at admission

Antecedentes y objetivoEl cuestionario “Structured HIstory of Medication use” (SHIM) es una herramienta diseñada para obtener una visión completa de la medicación del paciente antes del ingreso mediante una entrevista estructurada, y ha demostrado su potencial para prevenir errores de conciliación. El objetivo de este estudio fue adaptar transculturalmente el cuestionario SHIM al español.Pacientes y métodosTraducción directa e inversa seguidas de una síntesis y adaptación, que contó con la participación de un panel de expertos, para garantizar la equivalencia entre el cuestionario original y su versión española. Posteriormente se realizó un análisis de la comprensibilidad de la versión española del cuestionario mediante entrevistas cognitivas en una muestra de pacientes polimedicados en seguimiento por el Servicio de Medicina Interna.ResultadosSe obtuvo la versión española del cuestionario SHIM (SHIM-e). El grado de dificultad asignado por los traductores a la traducción directa e inversa fue bajo. Durante la fase de síntesis y adaptación se resolvieron tres discrepancias y se decidió emplear, en la versión del cuestionario adaptada al español, algunos términos de uso común en la entrevista clínica. El análisis de la comprensibilidad, realizado en una muestra de 10 pacientes polimedicados e ingresados en la Unidad de Cirugía General y de Aparato Digestivo, mostró una comprensibilidad del 100% para todos los ítems, excepto para el número 13 que fue del 90%.ConclusionesEste trabajo presenta la primera adaptación transcultural al español del cuestionario SHIM. Los procesos de traducción directa e inversa han presentado una dificultad baja y los resultados de las entrevistas cognitivas muestran un nivel alto de comprensibilidad para la versión española de esta herramienta.

Cross-cultural adaptation to the Spanish version of the "Structured HIstory of Medication Use" questionnaire for medication reconciliation at admission. / Adaptación transcultural a la versión española del cuestionario "Structured HIstory of Medication Use" para la conciliación de la medicación al ingreso.

BACKGROUND AND OBJECTIVE: The "Structured HIstory of Medication use" (SHIM) questionnaire is a tool developed to obtain an accurate pre-admission overview of medications, involving a structured interview with patients, and has demonstrated its potential to prevent reconciliation errors. The objective of this study was to cross-culturally adapt the SHIM questionnaire to Spanish. PATIENTS AND METHODS: Forward and blind-back translations followed by a synthesis and adaptation, with the participation of an expert panel, to guarantee the equivalence between the original questionnaire and the Spanish version. Subsequently, pilot testing of the Spanish version was carried out through cognitive interviews in a sample of polymedicated patients under follow-up by the Department of Internal Medicine. RESULTS: The Spanish version of the SHIM questionnaire (SHIM-e) was obtained. Scores for difficulty assigned by translators involved in forward and back translations were low. During the synthesis and adaptation phase, three discrepancies were resolved, and the expert panel decided to include some terms commonly used for clinical interviews in the Spanish version of the questionnaire. The pilot testing, which was performed in a sample of 10 polymedicated patients admitted to the Department of General and Digestive Surgery, showed 100% comprehensibility for all items, except for number 13, which was 90%. CONCLUSIONS: This work presents the first cross-cultural adaptation to Spanish of the SHIM questionnaire. The forward and blind-back translations presented low difficulty and the results of the pilot testing showed a high level of comprehensibility for the Spanish version of this tool.

Concordance Among 10 Different Anticholinergic Burden Scales in At-Risk Older Populations.

OBJECTIVE: The aim of the study was to evaluate the concordance among 10 anticholinergic scales for the measurement of anticholinergic drug exposure in at-risk elderly complex chronic patients in primary care. METHODS: An 8-month cross-sectional, multicenter study was carried out in a cohort of complex chronic patients older than 65 years in treatment with at least 1 drug with anticholinergic activity. Demographic, pharmacological, and clinical data were collected. Anticholinergic burden and risk were detected using the 10 scales included on the anticholinergic burden calculator (http://www.anticholinergicscales.es/). We used κ statistics to evaluated the concordance 2 to 2 (according to risk: high, medium, low or without risk) among the included scales. RESULTS: Four hundred seventy-three patients were recruited (60.3% female, median age of 84 years [interquartile range = 10]). Eighty was the total number of anticholinergic drugs with any scale (1197 prescriptions), with a median of 2 drugs with anticholinergic activity per patient (interquartile range = 2). The κ statistics comparing all the 10 scales ranged from -0.175 (Drug Burden Index versus Chew Scale) to 0.708 (Anticholinergic Activity Scale [AAS] versus Chew Scale). The best concordance was obtained between AAS and Chew Scale (κ = 0.708), followed by Clinician-Rated Anticholinergic Scale and Duran Scale (κ = 0.632) and AAS and Anticholinergic Cognitive Burden Scale (κ = 0.618), being considered substantial strengths of concordance. CONCLUSIONS: The agreement among the 10 scales in elderly patients with complex chronic conditions was highly variable. Great care should be taken when assessing anticholinergic drug exposure using existing scales because of the wide variability among them. The only scales that showed agreement were the AAS-Chew, Clinician-Rated Anticholinergic Scale-Duran, and AAS-Anticholinergic Cognitive Burden Scale pairs. In the rest of the cases, the scales are not interchangeable.

Impact on daily clinical practice of the latest evidence on percutaneous closure of patent foramen ovale after cryptogenic stroke: a single-center experience.

INTRODUCTION AND OBJECTIVES: At the end of 2017, three clinical trials demonstrated that, in selected patients, percutaneous closure of patent foramen ovale (PFO) after cryptogenic stroke (CS) reduces the risk of recurrence. Our aim was to determine the impact of these findings on routine clinical practice in a tertiary hospital. METHODS: Patients with CS and percutaneous closure of PFO during 2001-2020 were included. The clinical characteristics of the patient and the anatomical characteristics of the foramen were analyzed. Based on both, the closure indications were classified into three groups according to the latest European recommendations and were analyzed in two periods, before and after the publication date of the clinical trials. RESULTS: A total of 293 patients were included. The mean age was 49 ± 11 years, and 15% were older than 60 years. The median RoPE score was 6 [p25-75, 5-7] and 75% had complex anatomy (CA). After the publication of the studies, the frequency of CA and the mean age of the patients were significantly higher (89% vs. 69% p < 0.0005 and 51 ± 11 vs. 48 ± 11 years, p = 0.02, respectively), and the RoPE score, significantly lower (5 [5-7] versus 6 [5-7], p = 0.02). Inadequate closure indications were significantly reduced (8% vs. 18%, p = 0.02). CONCLUSION: After the publication of clinical trials that have shown benefit of PFO closure after CS, the number of inappropriate indications for closure has decreased significantly in our institution, with a higher percentage of CA, despite a clinical profile suggestive of lower causal probability of PFO.

Estimating the annual economic burden for the management of patients with transthyretin amyloid polyneuropathy in Spain.

Background: Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal disease associated with substantial burden of illness. Three therapies are approved by the European Medicines Agency for the management of this rare disease. The aim of this study was to compare the total annual treatment specific cost per-patient associated with ATTR-PN in Spain.Methods: An Excel-based patient burden and cost estimator tool was developed to itemize direct and indirect costs related to treatment with inotersen, patisiran, and tafamidis in the context of ATTR-PN. The product labels and feedback from five Spanish ATTR-PN experts were used to inform resource use and cost inputs.Results: Marked differences in costs were observed between the three therapies. The need for patisiran- and inotersen-treated patients to visit hospitals for pre-treatment, administration, and monitoring was associated with increased patient burden and costs compared to those treated with tafamidis. Drug acquisition costs per-patient per-year were 291,076€ (inotersen), 427,250€ (patisiran) and 129,737€ (tafamidis) and accounted for the majority of total costs. Overall, the total annual per-patient costs were lowest for patients treated with tafamidis (137,954€), followed by inotersen (308,358€), and patisiran (458,771€).Conclusions: Treating patients with tafamidis leads to substantially lower costs and patient burden than with inotersen or patisiran.

Utility of a trigger tool (TRIGGER-CHRON) to detect adverse events associated with high-alert medications in patients with multimorbidity.

OBJECTIVE: To determine the utility of a tool (TRIGGER-CHRON) for identifying adverse drug events (ADEs) associated with the administration of high-alert medications in elderly patients with multimorbidity and to determine the medications most frequently implicated. METHODS: A retrospective observational study was conducted at 12 Spanish hospitals. A random sample of five medical records from each hospital was selected weekly for review over a 12-week period. We included patients aged 65 and over with multimorbidities, hospitalised for >48 hours. ADEs detected by the 32 TRIGGER-CHRON signals and caused by high-alert medications included on the Spanish HAMC list for chronic patients were selected for analysis. Triggers identified and ADEs detected were recorded. The severity and preventability of the ADEs were evaluated. The positive predictive value (PPV) of each trigger was calculated. RESULTS: On 720 charts reviewed, 908 positive triggers were identified that led to the detection of 158 ADEs caused by at least one high-alert medication on the HAMC list. These ADEs occurred in 139 patients (prevalence 19.3/100 admissions). The majority of ADEs were mild and 59.5% were deemed preventable. The drugs most frequently associated with ADEs were corticosteroids, loop diuretics, opioid analgesics and oral anticoagulants. Fifteen triggers had PPVs ≥20%. Six triggers (serum glucose >110 mg/dL, abrupt cessation of medication, oversedation/lethargy, hypotension, adverse reaction recorded and constipation) accounted for 69.8% of the ADEs identified. CONCLUSIONS: Applying the TRIGGER-CHRON to hospitalised patients with multimorbidity in 12 Spanish centres allowed detection of one adverse event caused by a high-alert drug for every four patients, which were preventable in a large proportion of patients. This confirms the need to establish interventions that reduce harm with these medications. We believe that TRIGGER-CHRON can be a useful tool to measure this harm and to determine the effects of medication safety improvement programmes as they are implemented.

Implementation of a novel home delivery service during pandemic.

INTRODUCTION: During the COVID-19 pandemic, measures have been put in place to adapt to patients' needs during home quarantine, such as "telehealthcare". With this service, hospital pharmacists develop a distinct role via the implementation of pharmacovigilance services and pharmaceutical care plans for patients with comorbidities, and for special populations as immunosuppressed patients.MethodsCross-sectional study involving hospital and community pharmacists actively practising during the COVID-19 pandemic. Patients who could not come to the hospital pharmacy department were provided with a delivery service to the community pharmacy of their choice. RESULTS: A total of 1186 patients requested this service. Erythropoiesis-stimulating agents were the most in-demand medication, followed by rheumatoid arthritis and antiretroviral drugs. 125 patients responded to the telephone survey, most of whom stated that they would use the delivery service again, and expressed their desire to continue doing so. DISCUSSION: Without a doubt, telepharmacy and medication delivery services have provided multiple benefits during home quarantine. The delivery service enabled us to provide drugs to patients in their immediate environment through a service that was free for both the patient and the hospital pharmacy service. However, at present, the available evidence of the impact of telepharmacy models is sparse. CONCLUSIONS: This medication delivery service has provided multiple benefits to patients during home quarantine. Although the users of this service seem to be satisfied with the current model, in the future, we should consider which patients would benefit most from this service and shape it to individual needs.

Mapa de unidades de farmacocinética y farmacogenética clínica en España / Mapping the clinical pharmacokinetics and pharmacogenetic units operating in Spanish hospitals

Objetivo: Dar a conocer la actividad asistencial y docente de las unidades de farmacocinética y farmacogenética de los servicios de farmaciahospitalaria españoles y elaborar un mapa que refleje la situación actual.Método: Se diseñó una encuesta de 29 preguntas estructuradas encinco bloques: datos generales del hospital e información sobre la actividad asistencial y docente, tanto en el área de farmacocinética como defarmacogenética en los servicios de farmacia hospitalaria.Resultados: Respondieron la encuesta 69 hospitales. Las regiones geográficas con mayor número de respuestas fueron Cataluña, ComunidadValenciana y Andalucía. Los grupos farmacológicos que más se monitorizaron fueron los antibióticos clásicos (vancomicina y aminoglucósidos) (93%),digoxina (57%), antiepilépticos clásicos (51%) y biológicos (43%). Los programas informáticos que con más frecuencia se utilizaban fueron PKS yNONMEM, con un 93% y 22%, respectivamente. Respecto a la docenciaen farmacocinética, fue el segundo año de residencia cuando la mayoría delos farmacéuticos internos residentes rotaban por el área (40%) y un 44%de las unidades permitían rotantes externos. El responsable de la farmacogenética era el servicio de farmacia hospitalario en un 43% de los casos.Los ámbitos más frecuentes fueron oncohematología (72%) y psiquiatría(15%). Un 24% de los hospitales ofrecían rotación por la unidad de farmacogenética y sólo 7 servicios de farmacia ofertaron rotaciones externas. Conclusiones: Los resultados de la encuesta mostraron un incremento enla realización de actividades de farmacocinética y farmacogenética en losservicios de farmacia hospitalaria comparados con los datos de la encuesta basal de 2009. (AU)

Objective: The goal of this article is to analyze the situation of pharmacokinetics and pharmacogenetics units in the pharmacy departmentsof Spanish hospitals, evaluate their development both in the clinical andeducational areas, and draw up a map reflecting their current status.Method: A 29-item survey structured in five blocks was designed withgeneral questions about the respondents’ hospital and the clinical andeducational activities carried out by their pharmacy department, in thefields of both pharmacokinetics and pharmacogenetics.Results: Sixty-nine hospitals answered the survey. The highest response ratescorresponded to Catalonia, the Valencia region and Andalusia. The drugfamilies subject to closest monitoring were classic antibiotics (93%), digoxin(57%), classic antiepileptics (51%) and biologicals (43%). The most frequentlyused computer programs included PKS and NONMEM (93% and 22% ofhospitals, respectively). Regarding training in pharmacokinetics, second yearresidents were those who most frequently rotated through the pharmacokinetics unit (40%), while 44% of those units allowed external residents. Asfar as pharmacogenetics is concerned, in 42% of hospitals that engaged inpharmacogenetic work, the department in charge was pharmacy. The mostfrequent specialties covered were hemato-oncology (72%) and psychiatry(15%). Twenty-four percent of hospitals offered rotations through their pharmacogenetics unit but only seven of them allowed external residents.Conclusions: The results of the survey showed an increase in the performance of pharmacokinetic and pharmacogenetic activities by Spanishhospital pharmacies as compared with the data from a 2009 baseline survey, with many hospitals introducing the performance of therapeutic drugmonitoring of non-classical antibiotics, immunosuppressants and biologics. (AU)

Intrafollicular and Systemic Dopamine, Noradrenaline and Adrenaline Concentrations in Cycling Mares.

In some species, catecholamines in follicular fluid (FF) are related to local physiological events responsible for the regulation of ovarian functions and oocyte maturation. The aim of the present study was to determine and compare intrafollicular and systemic concentrations of dopamine (DA), noradrenaline (NA) and adrenaline (AD) in cycling mares. Sixty ovaries were collected during breeding season from 30 mares raised for slaughterhouse meat production, with clinically normal reproductive tracts, were evaluated. Blood samples were collected prior to slaughter. Follicles were classified into three categories in relation to size: small (20-30 mm; n = 20), medium (≥31-40 mm; n = 20) and large (≥41 mm; n = 20). Follicular fluid (FF) samples were extracted from each follicle. Intrafollicular DA, NA and AD concentrations were significantly higher than the systemic concentrations (p < 0.05). Intrafollicular DA concentrations were higher in medium than small and large follicles (p < 0.05). Intrafollicular NA concentrations were higher in small than medium and large follicles (p < 0.05). Intrafollicular AD concentrations were higher in large than small and medium follicles (p < 0.05). Follicle diameter was significantly and negatively correlated with NA and AD (p < 0.05). A significant correlation of the same hormone concentration in FF and in systemic fluid was observed (p < 0.05). In summary, the FF can serve as an intraovarian catecholamine-storing compartment, with the ability to release neurotransmitters in a regulated way. These results provide novel insights into the neuronal nature of the follicle, suggesting the involvement of catecholamines in normal ovarian functions in mares.

Development and psychometric study of a simple instrument to assess patient communication and comprehension skills: the AsCkS.

BACKGROUND: Instruments to examine patients' communication skills are impractical for daily clinical practice in primary health care, and it is assumed that health care professionals are always aware of the communication and comprehension status of patients. OBJECTIVE: To design and examine the psychometric properties of a new questionnaire (AsCkS) to screen patients' risk of low communication and comprehension skills. METHODS: Designing the new questionnaire involved: (i) a content validity study to generate a set of items, (ii) administration of a questionnaire in a sample of patients and (iii) study of the psychometric properties using a Rasch probabilistic model. The test probability function was used to detect patients at risk of having low communication and comprehension skills, and the associated factors were studied using multivariate logistic regression. RESULTS: Five items were generated and 369 patients screened. In the Rasch analysis, one item was removed due to a lack of goodness-of-fit (Outfit = 3.64). The final set of four items showed good reliability (person separation index = 0.90). Convergent validity was moderate for the health literacy construct (r = 0.53) and low for the patient activation (r = 0.38): 77 patients (20.86%) were at risk of having low communication and comprehension skills. After adjustment, the associated factors were age (p < 0.001) and lower educational level (p < 0.001). CONCLUSION: The AsCkS is a reliable and valid instrument and may be used to detect patients requiring a greater effort by the physician to communicate health care messages.

A very mild phenotype of Charcot-Marie-Tooth disease type 4H caused by two novel mutations in FGD4.

BACKGROUND: Mutations in the FGD4 gene cause an autosomal recessive demyelinating peripheral neuropathy referred to as CMT4H, characterized by its onset in infancy or early-childhood and its slow progression. METHODS: The clinical and genetic status of two patients with CMT4H was studied, performing genetic testing with a panel of genes and analysing FGD4 mRNA expression by quantitative PCR. RESULTS: Two novel FGD4 variants (c.514delG and c.2211dupA) were identified in two mildly affected Spanish siblings with CMT4H, and with disease onset in late adolescence/adulthood (one of them remaining asymptomatic at 20). On examination, foot deformity was observed without weakness or sensory involvement, and in the muscles of the lower extremities magnetic resonance imaging showed no fat replacement. Further analysis of FGD4 expression in peripheral blood suggested that neither mutation affected splicing, nor did they affect the dosage of FGD4 mRNA (compared to a healthy control). It was predicted that each allele would produce a truncated protein, p.Ala172Glnfs*28 (c.514delG) and p.Ala738Serfs*5 (c.2211dupA), the latter containing all the functional domains of the native protein. CONCLUSIONS: The conservation of functional domains in the proteins produced from the FGD4 gene of two patients with CMT4H, could explain both the milder phenotype and the later disease onset in these patients. These results expand the clinical and mutational spectrum of FGD4-related peripheral neuropathies.