Integration of persistence in the 5P-medicine approach for age-related chronic diseases.

5P medicine is defined as Personalized, Predictive, Preventive, Participatory, and Population-based. 5P medicine may be improved by including a factor that could provide information about the therapeutic value of a particular drug treatment and measure its effectiveness in clinical practice. We propose that this factor may be treatment persistence, and that its addition to 5P medicine would allow to define a new improved 6P medicine. Persistence is the length of time between initiation and the last dose, which immediately precedes discontinuation, that is, a definitive suspension of the treatment. By including this sixth P, the persistence, we would be able to present the value of a treatment for each individual patient with its own characteristics, state of the disease, with more than one age-related diseases and patient journey. Persistence is a concept of the value of a treatment that includes the three main stakeholders of the pharmacotherapeutic process: Patient, Physician, and Pharmacist. Persistence is becoming a useful measure to evaluate the long-term effectiveness of therapies in real-world setting in chronic diseases. Drug treatments with longer persistence are more likely to provide better disease control and to be amenable to dose adjustment in order to optimize treatment cost in age-related chronic diseases. Long-term persistence could be a measure of a drug´s real-world performance and has been shown to aid in clinical decision-making.

Risk-sharing agreement based on health outcomes for the treatment of moderate-severe psoriasis with certolizumab pegol. / Acuerdo de riesgo compartido basado en resultados de salud para el tratamiento de psoriasis moderada-grave con certolizumab pegol.

OBJECTIVE: To provide evidence of the effectiveness of certolizumab pegol (CZP) in real clinical practice in adult patients with moderate-to-severe plaque psoriasis (PsO) in the context of a risk-sharing agreement (RSA). METHODS: Retrospective observational study based on variables collected in the RSA for treatment with CZP of adult patients with moderate-severe plaque PsO. Ten Spanish hospitals where the RSA was implemented participated. The percentage of patients who achieved the target clinical response of the RSA at the follow-up visit (week 16) was evaluated: absolute Psoriasis Area and Severity Index (PASI) value ≤3 for biologic naïve population, and ≤5 in case of previous failure to a single biologic drug. In addition, the improvement in the scores of other scales included in the study was analyzed: Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), Physician's Global Assessment (PGA), and Nail Psoriasis Severity Index (NAPSI). A descriptive analysis was performed for the total population and by patient subgroups (naive vs. non-naive to biologic, male vs. female, and with vs. without discontinuation). RESULTS: Sixty-six patients were included, 12 men and 54 women. 90.9% achieved the target clinical response, with a mean reduction of 8 (-78.4%) absolute PASI points. Improvement was observed in BSA, PGA, NAPSI and DLQI, with a reduction of 11.3 (-80.6%), 1.9 (-65.5%), 3.3 (-30.7%) and 9.0 (-66.4%) absolute value points, respectively. Despite not achieving the therapeutic target set in the RSA in six patients (9%) (the cost of the drug was assumed by the laboratory), only two (3%) discontinued treatment. CONCLUSION: Our study shows that CZP is effective in real clinical practice in patients with moderate-severe plaque PsO, with an improvement in absolute PASI and DLQI, as well as other scales, both for the total population and in the subgroups analyzed. Nearly 91% of patients reached the therapeutic target fixed in the RSA. Implementing this type of agreement can provide a direct or indirect benefit for all the agents involved in the process, providing valuable information for decision-making.

A computer architecture based on disruptive information technologies for drug management in hospitals.

The drug management currently carried out in hospitals is inadequate due to several factors, such as processes carried out manually, the lack of visibility of the hospital supply chain, the lack of standardized identification of medicines, inefficient stock management, an inability to follow the traceability of medicines, and poor data exploitation. Disruptive information technologies could be used to develop and implement a drug management system in hospitals that is innovative in all its phases and allows these problems to be overcome. However, there are no examples in the literature that show how these technologies can be used and combined for efficient drug management in hospitals. To help solve this research gap in the literature, this article proposes a computer architecture for the whole drug management process in hospitals that uses and combines different disruptive computer technologies such as blockchain, radio frequency identification (RFID), quick response code (QR), Internet of Things (IoT), artificial intelligence and big data, for data capture, data storage and data exploitation throughout the whole drug management process, from the moment the drug enters the hospital until it is dispensed and eliminated.

Consensus of Spanish Society of Hospital Pharmacy on optimal medication therapy management of atopic dermatitis. / [Artículo traducido] Consenso de la Sociedad Española de Farmacia Hospitalaria sobre el manejo fármacoterapéutico óptimo de la dermatitis atópica.

AIM: This study's aims are: 1) To use the Delphi method to determine the level of consensus among HPs as regards the factors involved in the current approach to patients with AD; 2) To identify potential areas for improvement in hospital pharmacy in terms of dealing with patients with severe AD; and 3) To contribute to adequate pharmaceutical care for patients with AD by drawing up recommendations. METHODS: A two-round Delphi survey with participation from HPs from all over Spain. Three theme-based blocks were set out: 1) AD; 2) Management of patients with severe AD in the Hospital Pharmacy setting; and 3) Unmet needs (pathology, patient, treatment and management). RESULTS: The 42 HPs participating reached a consensus in recognizing the impact of severe AD on the patients suffering from it, the need to encourage adherence and the recommendations to use scales that take into account the patient's quality of life and indicators of the patient's experience. It has also been demonstrated that it is worthwhile evaluating the results in real clinical practice in consensus with other specialists from the multidisciplinary team. Finally, it is advisable to use drugs that have demonstrated long-term effectiveness and safety for patients with severe AD, given the disease´s chronic nature. CONCLUSIONS: This Delphi consensus highlights the impact of severe AD on patients, the importance of a multidisciplinary and holistic approach, in which HP play a major role. It also highlights the importance of increased access to new drugs to improve health outcomes.

Consensus of Spanish Society of Hospital Pharmacy on optimal medication therapy management of atopic dermatitis.

AIM: This study's aims are: 1) To use the Delphi method to determine the level of consensus among hospital pharmacists (HPs) as regards the factors involved in the current approach to patients with atopic dermatitis (AD); 2) To identify potential areas for improvement in hospital pharmacy in terms of dealing with patients with severe AD; and 3) To contribute to adequate pharmaceutical care for patients with AD by drawing up recommendations. METHODS: A two-round Delphi survey with participation from HPs from all over Spain. Three theme-based blocks were set out: 1) AD; 2) Management of patients with severe AD in the Hospital Pharmacy setting; and 3) Unmet needs (pathology, patient, treatment and management). RESULTS: The 42 HPs participating reached a consensus in recognising the impact of severe AD on the patients suffering from it, the need to encourage adherence and the recommendations to use scales that take into account the patient's quality of life and indicators of the patient's experience. It has also been demonstrated that it is worthwhile evaluating the results in real clinical practice in consensus with other specialists from the multidisciplinary team. Finally, it is advisable to use drugs that have demonstrated long-term effectiveness and safety for patients with severe AD, given the disease's chronic nature. CONCLUSIONS: This Delphi consensus highlights the impact of severe AD on patients, the importance of a multidisciplinary and holistic approach, in which HP play a major role. It also highlights the importance of increased access to new drugs to improve health outcomes.

Therapeutic Drug Monitoring in Oncohematological Patients: A Fast and Accurate HPLC-UV Method for the Quantification of Nilotinib in Human Plasma and Its Clinical Application.

Nilotinib, a second-generation tyrosine kinase inhibitor, has demonstrated clinical activity in chronic myeloid leukemia. As an exposure-response relationship has been observed for nilotinib, its therapeutic drug monitoring could be a valuable tool in clinical practice. Therefore, the aim of this study was to develop and validate a selective and precise high performance liquid chromatography-ultraviolet method for the measurement of nilotinib in plasma from patients with cancer. After protein precipitation extraction with acetonitrile, nilotinib and rilpivirine were separated using isocratic elution on a Tracer Excel 120 ODS C18 column using a mobile phase consisting of a mixture of potassium dihydrogen phosphate-buffered solution (pH 5.5; 0.037 M)-methanol-acetonitrile (45:45:10, v/v/v), pumped at a flow rate of 1.7 mL·min-1. A wavelength of 254 nm was selected for the quantification of the analyte and the internal standard (IS). The technique was validated following the guidelines for the validation of analytical methods of regulatory agencies (Food and Drug Administration (FDA) and the European Medicines Agency (EMA)). Linearity was established in a concentration range between 125 and 7000 ng/mL. The detection limit was 90 ng/mL, and the lower limit of quantification was 125 ng/mL. For all concentrations in the calibration curve, the intraday and interday coefficients of variation were less than 4.1%. Median recovery of nilotinib from plasma was ≥65.1% (±21.4%). The method described is sensitive, selective, reproducible, and rapid, and can be used for the accurate determination of nilotinib in human plasma for pharmacokinetics studies and for therapeutic drug monitoring (TDM) of nilotinib in routine clinical practice.

Six months multicentre pilot open label single-arm study to evaluate patient experience, acceptability and satisfaction of switching certolizumab pegol from a prefilled syringe or autoinjection pen to an AVA® e-Device in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis patients.

WHAT IS KNOWN AND OBJECTIVE: The study aimed to assess acceptability and patient experience of Certolizumab (CZP) self-injection with AVA® and clarify patient device preference after switching CZP from the syringe or auto-injection pen to AVA® in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients. METHOD: A multicentre open-label, cross-sectional and prospective study among four Spanish hospitals was performed. Adult RA, PsA, axSpA patients treated for at least 6 months with the CZP syringe or pen were recruited. At the first visit, patients completed Pre-AVA® questionnaire. Patients were instructed on proper administration of CZP by AVA®. After 2 and 6 months of CZP self-injections using the AVA®, patient experience, adherence, preference and safety of each administration was assessed using post-AVA® questionnaire. RESULTS AND DISCUSSION: Thirty four patients were included (28 women). All patients self-administered CZP AVA® the full dose of CZP was injected. Patients reported >90% adherence to CZP AVA® assessed with the injection log. Pain at the injection site was reduced after switching to AVA®. Twenty nine patients preferred CZP AVA® and five patients preferred the CZP pen. No safety-related findings related to AVA® CZP administration were identified. WHAT IS NEW AND CONCLUSION: The AVA® is an advantageous delivery option for CZP in patients with RA, PsA, axSpA.

Clinical Impact of the Capacity-Motivation-Opportunity Pharmacist-Led Intervention in People Living with HIV in Spain, 2019-2020.

Background: People living with HIV (PLWH) have significantly enhanced their life expectancy. Consequently, age-associated comorbidities and related health conditions are increasingly found in PLWH complicating their clinical management. Objective: To determine the effect of the capacity-motivation-opportunity (CMO) structured pharmaceutical care intervention for improving clinical health-care results frequently associated to PLWH. Methods: Multicenter, prospective, pre-post intervention study evaluating the CMO pharmacist-led program in adult PLWH was conducted between September 2019 and September 2020 with six months of follow-up. The primary objective of this study was to determine differences in clinical outcomes (total cholesterol, triglycerides, HDL, blood pressure and glycosylated hemoglobin) and variation in the patient's activation measure before and after the intervention. Results: A total of 61 patients were included, 72% were men with a median age of 53 years. After the implementation of the pharmacist-driven program, the percentage of patients with high levels of total cholesterol decreased significantly (18% to 4.9%; p < 0.001). Similarly, the prevalence of patients with high levels of triglycerides, HDL or with hypertension was significantly lower post intervention (13.1% to 6.6%, p < 0.001; 47.5% to 6.6%, p = 0.019 and 24% to 4%, p = 0.009, respectively). The number of patients who achieved the highest activation level increased from 69% to 77.6% (p < 0.001). Conclusion: The CMO program resulted in significantly better health outcomes during the six months following the pharmacist-led intervention as well as improved activation in PLWH.

Application of the CMO methodology to the improvement of primary adherence to concomitant medication in people living with-HIV. The PRICMO Project.

OBJECTIVE: To determine the effectiveness of a pharmaceutical care intervention based on the CMO methodology (Capacity, Motivation  and Opportunity) in improving primary adherence to concomitant  treatment in HIV+ patients on antiretroviral treatment. METHOD: This was a longitudinal prospective multicenter study carried out  between September 2019 and September 2020, which included HIV+  patients older than 18 years who were on antiretroviral treatment and  were taking concomitant medications. Demographic, clinical, and pharmacotherapeutic variables were collected. As required by the CMO methodology, all patients were followed for 6 months and stratified  into three levels of care. Individualized pharmaceutical care was provided according to the interventions established for each level. At every consultation, a motivational interview was conducted based on each  patient's alignment with and achievement of their pharmacotherapeutic  objectives. A website was developed to deal with the opportunity pillar.  The main variable was the percentage of patients considered primary  adherents to the prescribed concomitant medication. Adherence over the  six months prior to the study was compared to adherence at the end of the study. Additionally, the percentage of patients considered secondary  adherents to concomitant treatment and antiretroviral treatment during  the 6 months prior to the start of the study was compared to the  percentage of such patients at the end of the study. Adherence was  measured based on dispensation records and specific validated  questionnaires. Patients were only considered adherent if they were  deemed adherent by both methods. RESULTS: A total of 61 patients were included in the study, 72% male. Median age was 53 years and the median number of concomitant drugs prescribed was 7. A total of 60.6% of patients were polymedicated. The percentage of patients considered primary non-adherent was 52.5% at baseline (n = 32) and 4.9% (n = 3, p < 0.001) at the end of the study. Secondary adherence to both concomitant medication (41.6% vs 88.3%) and antiretroviral treatment (85.2% vs 95.1%) improved at the end of the study (p < 0.0001). CONCLUSIONS: Pharmaceutical care based on the CMO methodology significantly improved both primary and secondary  dherence to concomitant drugs and to antiretroviral treatment.

Objetivo: Determinar la efectividad de una intervención farmacéutica, basada en la metodología CMO (Capacidad, Motivación,  portunidad), para mejorar la adherencia primaria al tratamiento  concomitante en pacientes VIH+ en tratamiento antirretroviral.Método: Estudio longitudinal, prospectivo, multicéntrico, realizado entre septiembre de 2019 y septiembre de 2020. Se incluyeron pacientes VIH+ mayores de 18 años, en tratamiento antirretroviral y  prescripción de fármacos concomitantes. Se recogieron variables  demográficas, clínicas y farmacoterapéuticas. Se realizó atención  farmacéutica durante 6 meses según el modelo CMO en cada paciente,  basado en su nivel de estratificación y las intervenciones establecidas para cada umbral. En cada consulta se realizó una entrevista motivacional  basada en el alcance de los objetivos farmacoterapéuticos para cada  paciente. Para desarrollar el pilar de oportunidad se creó y desarrolló la  web: www.proyecto-pricmo.com. La variable principal fue el porcentaje de  pacientes considerados adherentes primarios a la medicación concomitante  prescrita, comparando los 6 meses previos al estudio, frente al mismo valor al finalizar el estudio. Adicionalmente, se comparó el  porcentaje de pacientes adherentes secundarios al tratamiento  concomitante y al tratamiento antirretroviral durante los 6 meses previos  al inicio del estudio frente al mismo valor en los pacientes al finalizar el  estudio. Para medir la adherencia se consideraron dos métodos: registros  y cuestionarios validados específicos. Solo se consideraron adherentes si lo fueron a ambos métodos.Resultados: Se incluyeron 61 pacientes. El 72,0% fueron hombres, con una mediana de edad de 53 años. La mediana de fármacos  oncomitantes fue de 7. El 60,6% de los pacientes tenían presencia de  polifarmacia. El porcentaje de pacientes considerados no adherentes  primarios basalmente fue del 52,5% (n = 32), mientras que a la  finalización fue del 4,9% (n = 3, p < 0,001). Tanto la adherencia  secundaria a la medicación concomitante (41,6% versus 88,3%) como al  tratamiento antirretroviral (85,2% versus 95,1%) mejoraron al finalizar el  estudio (p < 0,001).Conclusiones: La intervención farmacéutica basada en la metodología CMO mejoró significativamente tanto la adherencia primaria  como secundaria a la medicación concomitante y la secundaria al  tratamiento antirretroviral.

Effect of Early Peripheral Parenteral Nutrition Support in an Enhanced Recovery Program for Colorectal Cancer Surgery: A Randomized Open Trial.

BACKGROUND: Peripheral parenteral nutrition allows repletion of acute nutrient deficiencies and could prevent further nutrition deficits before and after colorectal surgery. A randomized open study was performed to evaluate the effect of perioperative peripheral parenteral nutrition (PPN) support on postoperative morbidity after colorectal cancer surgery within an enhanced recovery program. METHODS: Patients were randomized into two groups: peripheral parenteral nutrition (PPN) (with Peri-Olimel N4-E) versus conventional fluid therapy (FT). Ninety-day postoperative complications, laboratory parameters, length of hospital stay, and compliance with the ERAS protocol were assessed. RESULTS: A total of 158 patients were analysed. The overall 90-day complication rate was 38.6% (61 patients), and 24 patients had major complications (Clavien-Dindo III-V) (15.2%). In the multivariate analysis, the intervention (PPN vs. FC) showed a protective effect against postoperative complications (p = 0.0031, OR = 0.2 (CI: 0.08-0.87)). Following ordinal regression, PPN and early oral tolerance showed a protective effect, being less likely to develop complications or to move from minor to major complications. In patients with low compliance to ERAS during the first postoperative day, PPN showed a protective effect, preventing 28% of morbidity. CONCLUSIONS: Perioperative peripheral parenteral nutrition (PPN) support with Peri-Olimel N4-E in colorectal cancer surgery associated with early oral intake could reduce postoperative complications.

Health and economic impact of the correct diagnosis of transthyretin cardiac amyloidosis in Spain.

Objective: To estimate the health and economic impact of the reduction in mortality and cardiovascular hospitalizations, associated with correct diagnosis of cardiac transthyretin amyloidosis (ATTR-CM), from the Spanish National Health System (NHS) perspective.Methods: A costs and effects analysis were performed (probabilistic Markov model) with time horizons between 1 and 15 years, comparing the correct diagnosis of ATTR-CM versus the non-diagnosis. Transition probabilities were obtained from the ATTR-ACT study (placebo arm) and from the literature. Costs and healthcare resources were obtained from Spanish sources (€ 2019) and from a panel of Spanish clinical experts.Results: After 1, 5, 10 and 15 years, the diagnosis of ATTR-CM would generate a gain of 0.031 (95%CI 0.025; 0.038); 0.387 (95%CI 0.329; 0.435); 0.754 (95%CI 0.678; 0.781) and 0.944 (95%CI 0.905; 0.983) life years per patient, respectively, with savings of € 212 (95%CI € -632; 633), € 2,289 (95%CI € 2,250; 2,517), € 2,859 (95%CI € 2,584; 3,149) and € 2,906 (95%CI € 2,669; 3,450) per patient, respectively, versus the non-diagnosis.Conclusions: Just by correctly diagnosing ATTR-CM, years of life would be gained, cardiovascular hospitalizations would be avoided, and savings would be generated for the NHS, compared to the non-diagnosis of the disease.

Consensus to identify the dangerous drugs risks in hospital pharmacy services.

OBJECTIVE: To identify the hazards and define the theoretical  occupational risks arising from the process of handling hazard drugs in  hospital pharmacy services on the basis of expert consensus. METHOD: An expert consensus was conducted (nominal group and documentary techniques) using a mixed method of two face-to-face rounds (meeting of participants and approval of proposals) and  three masked rounds (individualized review). The analysis was applied  to the field of hospital pharmacy. The stages of the process were  designed using the standardized graphical Business Process Model and Notation. RESULTS: A specific flowchart was obtained for the management and  traceability of hazardous drugs. All general process phases were  characterized. A management chart included operations addressing the  reception and storage, compounding, conservation, and dispensation of  hazardous drugs in hospital pharmacy services. This chart provides a  description of the chemical hazards and exposure routes. CONCLUSIONS: The hazardous drug process should be integrated in a standard management system to improve the safety of patients and  healthcare professionals. Efficiency can maximized and procedural  incidents minimized, thereby ensuring the quality and the safety of  hazardous drugs handling in hospital pharmacy services. Once hazards  are identified, risk assessment should be implemented using a  systematic and preventative methodology to minimize the risk and  severity of any adverse event.

Objetivo: Identificar los peligros y definir los riesgos laborales teóricos derivados del proceso de manipulación de los medicamentos  peligrosos en los servicios de farmacia hospitalaria mediante un  consenso de expertos.Método: Se realizó un consenso de expertos (grupo nominal y técnicas documentales) utilizando un método mixto mediante dos  rondas presenciales (reunión de los participantes y aprobación de  propuestas) y tres rondas enmascaradas (revisión del material de forma individual). El análisis se aplicó al ámbito de la farmacia hospitalaria y  las etapas del proceso se diseñaron mediante notación gráfica  normalizada Business Process Modeling Notation.Resultados: Se obtuvo el diagrama de flujo específico para la gestión y trazabilidad de los medicamentos peligrosos, caracterizándose cada  una de las fases del proceso general, recopiladas en un cuadro de  gestión de etapas y operaciones de recepción y almacenamiento,  elaboración, conservación y dispensación de medicamentos peligrosos  en los servicios de farmacia hospitalaria, que sirvió para la posterior  descripción de riesgos químicos y vías de exposición.Conclusiones: Los medicamentos peligrosos deben integrarse en un sistema normalizado de gestión con el fin de mejorar la seguridad del paciente y de los profesionales sanitarios, a la vez que se maximizan la eficiencia de los recursos y minimizan los incidentes procesales,  garantizando la calidad y la seguridad del proceso de manipulación de  medicamentos peligrosos en los servicios de farmacia. Sería deseable,  una vez se han identificado los peligros, llevar a cabo una evaluación de  los riesgos siguiendo una metodología sistemática y de abordaje  preventivo que permita calibrar la probabilidad de ocurrencia y la  gravedad de cualquier suceso adverso.

Availability of Authorizations from EMA and FDA for Age-Appropriate Medicines Contained in the WHO Essential Medicines List for Children 2019.

Lack of age-appropriate commercially drug products availability is a common problem in pediatric therapeutics; this population needs improved and safer drug delivery. In addition, biopharmaceutic aspects, dosage requirements, and swallowing abilities demand pediatric forms different to adult formulations. The objective of this study was to evaluate the authorization availability from United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) of oral essential medicines for children and analyze its age-appropriateness for oral administration in children. All oral drugs from 7th List of Essential Medicines for Children by World Health Organization (WHO) were selected. Availability of commercial drug products was collected from OrangeBook, Spanish drug product catalogue, British electronic Medicines Compendium, and the International Vademecum. Tablets, effervescent tablets, and capsules were considered as not age-appropriate forms. Liquid forms, powder for oral suspension, mini tablets, granules, and soluble films were considered as age-appropriate forms due to their flexibility. More than 80% of the studied drugs possess a commercial authorization in oral forms in both EMA and FDA. Nevertheless, around 50% of these formulations are not age-appropriate for most pediatric groups. This study shows the lack of age-appropriate medicines for children. More efforts are needed to improve development and approval of pediatric medicines.

Adequacy of Parenteral Nutrition in Preterm Infants According to Current Recommendations: A Study in A Spanish Hospital.

BACKGROUND: In preterm infants, it is important to ensure adequate nutritional intake to accomplish foetal growth requirements. This study evaluated clinical practice regarding the prescription of parenteral nutrition in preterm infants in the neonatology unit of a tertiary hospital. METHODS: It was a retrospective observational study of a sample of preterm infants (n = 155) born between January 2015 and December 2017 who were prescribed parenteral nutrition. Compliance with the hospital's protocol and with the guidelines of the scientific societies American Society for Parenteral and Enteral Nutrition (ASPEN), European Society for Clinical Nutrition and Metabolism (ESPEN) and Spanish Society of Clinical Nutrition and Metabolism (SENPE) was evaluated. The differences in macronutrient intake and total duration of parenteral nutrition were analysed according to gestational age and birth weight. RESULTS: The established protocol was followed in a high percentage (95.5%-100%) except with respect to the initiation of supplying established trace elements (64.9%). Compliance with the recommendations set forth in the guidelines was between 82.1% and 100%, with the exception of the initial carbohydrate intake recommended by ASPEN and ESPEN, for which compliance was 8.3%. Lower gestational age and birth weight were correlated with longer duration of parenteral nutrition (p < 0.001). CONCLUSIONS: A lower gestational age and birth weight are related to a longer duration of parenteral nutrition. The results of this study demonstrate the importance of developing and evaluating protocols in clinical practice.

Midazolam and haloperidol for palliative sedation: physicochemical stability and compatibility of parenteral admixtures

This study was done to determine the time while the binary admixtures with midazolam and haloperidol drugs are administered by perfusion to the patients in the clinical routine. Samples with different concentrations of both drugs were prepared following the usual clinical practice. Solvents used were 0.9 % sodium chloride solution and 5% dextrose, and viaflo plastic bags were used as the containers of the admixtures. Samples were not protected from light and were stored at 20 ºC or at 4 ºC. Compatibility and physicochemical stability were studied by visual inspection, turbidity measurement, pH determination and ultraviolet detection high performance liquid chromatography (UV-HPLC) was used to determine midazolam and haloperidol concentrations. The assay was validated following the FDA and EMA guidelines. Darunavir was used as internal standard (IS). For the studied admixtures, turbidity measurements and pH determinations showed little changes in function of the time. Haloperidol and midazolam concentrations determined by HPLC are within the acceptable range of drug concentrations, which are considered stable for four days in case of admixtures stored at 20 ºC and for seven days for refrigerated admixtures. Taking into account the microbiological risk matrix, the compatibility and the chemical and microbiological stability of the midazolam and haloperidol in the co-administered admixtures in viaflo plastic bags with 0.9 % sodium chloride solution and 5% dextrose can be set as 48 hours when samples are stored at 20 ºC and one week if they are refrigerated.

Development and validation of a guide for the continuity of care in perioperative medication management.

BACKGROUND: Increased longevity and the prevalence of associated pathologies is leading to more hospital admissions involving chronic patients with multiple pathological problems. In orthopedic surgical patients, it is very important to individually evaluate the risk/benefit of maintaining or suppressing chronic medications. For certain medications, there are consensus recommendations, but for others, the available information may be limited or controversial. OBJECTIVE: To develop and validate a new guide for the continuity of care in perioperative medication management in older orthopedic surgical patients. MATERIALS AND METHODS: An expert pharmacist developed the guide by systematically reviewing each medication category according to the Anatomical Therapeutic Chemical (ATC) classification system. The Pharmacy and Therapeutics Committee at the Hospital General Universitario de Elche reviewed the guide. After a training course on the guide for pharmacists, the guide was validated by studying the interobserver variability between pharmacists as well as between each pharmacist and the expert pharmacist. Cohen's kappa index (κ) was applied to determine interrater reliability. RESULTS: The guide includes 51 therapeutic groups. Each ATC pharmacological subgroup is structured according to the benefits and risks of continuing therapy. When we compared each pharmacist's recommendations with those of the expert pharmacist, the kappa value was found to be 0.8 [95% CI (0.7, 0.9)], indicating almost perfect concordance (overall percentage agreement 89.3%). CONCLUSIONS: We developed a guide for the continuity of care in perioperative medication management to improve the rationalization of medicines in the perioperative environment. After the pharmacists had been trained, the guide was validated by demonstrating a high level of concordance among the pharmacists' recommendations. Formal training seems to be essential to ensure consistency in medical decisions. LEVEL OF EVIDENCE: IV (Oxford Centre for Evidence-Based Medicine. http://www.cebm.net/index.aspx?o=5653 ).

Biopharmaceutical optimization in neglected diseases for paediatric patients by applying the provisional paediatric biopharmaceutical classification system.

AIMS: Unavailability and lack of appropriate, effective and safe formulations are common problems in paediatric therapeutics. Key factors such as swallowing abilities, organoleptic preferences and dosage requirements determine the need for optimization of formulations. The provisional Biopharmaceutics Classification System (BCS) can be used in paediatric formulation design as a risk analysis and optimization tool. The objective of this study was to classify six neglected tropical disease drugs following a provisional paediatric BCS (pBCS) classification adapted to three paediatric subpopulations (neonates, infants and children). METHODS: Albendazole, benznidazole, ivermectin, nifurtimox, praziquantel and proguanil were selected from the 5th edition of the Model List of Essential Medicines for Children from the World Health Organization. Paediatric drug solubility classification was based on dose number calculation. Provisional permeability classification was based on log P comparison versus metoprolol log P value, assuming passive diffusion absorption mechanisms and no changes in passive membrane permeability between paediatric patients and adults. pBCS classes were estimated for each drug, according to different doses and volumes adapted for each age stage and were compared to the adult classification. RESULTS: All six drugs were classified into provisional pBCS in the three paediatric subpopulations. Three drugs maintained the same classification as for adults, ivermectin and benznidazole changed solubility class from low to high in neonates and proguanil changed from low to high solubility in all age stages. CONCLUSION: Provisional pBCS classification of these six drugs shows potential changes in the limiting factors in oral absorption in paediatrics, depending on age stage, compared to the adult population. This valuable information will aid the optimization of paediatric dosing and formulations and can identify bioinequivalence risks when comparing different formulations and paediatric populations.

Stability and compatibility of ondansetron with haloperidol in parenteral admixtures.

BACKGROUND: The chemical stability of coadministered ondansetron (OND) and haloperidol (HAL) in parenteral admixtures has not been described yet. OBJECTIVE: The aim of the present work is to study the chemical stability and the compatibility of OND and HAL admixtures. METHODS: Normal saline solution and dextrose were used to prepare the admixture solutions of the drugs; the materials of the containers were the original plastic bags of the diluents and the stability was studied at 20°C. Compatibility was studied by visual inspection of no colour change and turbidity or precipitation appearance. The concentration of the drugs was studied by ultraviolet detection high-performance liquid chromatography. The method was validated following the Food and Drug Administration and European Medicines Agency guidelines, and the assay enables the measurement of both drugs with a linear calibration curve (r=0.999) over the concentration range 10-100 µg/mL, with acceptable values of linearity, precision and accuracy. Darunavir was used as internal standard. RESULTS: Most of the admixtures have an adequate concentration until 24 hours(less than 10% of loss). 25% of the samples show a higher loss at 24 hours, and the chemical stability of these samples is 12 hours. CONCLUSIONS: The stability and compatibility of OND and HAL in the coadministered admixtures in Viaflo plastic bags with normal saline or dextrose are suggested at 12 hours.

Relationship between the rs1414334 C/G polymorphism in the HTR2C gene and smoking in patients treated with atypical antipsychotics. / Relación entre el polimorfismo rs1414334 C/G del gen HTR2C y tabaquismo en pacientes tratados con antipsicóticos atípicos.

An association has been found between the C allele of the rs1414334 polymorphism in the HTR2C gene and the metabolic syndrome in psychiatric patients. However, no study has yet evaluated whether this allele is associated with smoking. To assess this issue, therefore, we performed a cross-sectional study with a sample of 166 adult patients treated with atypical antipsychotics in 2012-2013 in a region of Spain. The primary variable was the presence of the C allele of the rs1414334 polymorphism in the HTR2C gene. Secondary variables were the number of pack-years (number of cigarettes per day x number of smoking years ÷ 20), age, gender, schizophrenia, years since diagnosis, metabolic syndrome criteria and SCORE. A stepwise binary logistic regression model was constructed to determine associations between primary and secondary variables and their area under the ROC curve (AUC) was calculated. Of the total sample, 33 patients (19.9%) had the C allele of the polymorphism analyzed. Mean cigarette consumption was 11.6 pack-years. The multivariate analysis showed the following factors as associated with the polymorphism: higher cigarette consumption, being a woman, and not having abdominal obesity. The AUC was 0.706. An association was found between increased cigarette consumption over the years and the presence of the C allele of the rs1414334 polymorphism in the HTR2C gene.

En pacientes psiquiátricos, otros autores han encontrado una asociación entre el alelo C del polimorfismo rs1414334 del gen HTR2C y el síndrome metabólico. Ninguno de ellos ha valorado si este alelo se asocia con el consumo de tabaco, por lo que se decidió realizar un estudio en una región española valorando esta cuestión. Estudio observacional transversal de una muestra de 166 pacientes adultos tratados con antipsicóticos atípicos en 2012-2013. Variable principal: presencia del alelo C del polimorfismo rs1414334 del gen HTR2C. Variables secundarias: número de años-paquete (número de cigarrillos al día x número de años fumando ÷ 20), edad, sexo, esquizofrenia, años diagnosticados del trastorno, criterios de síndrome metabólico y SCORE. Se construyó un modelo de regresión logística binaria por pasos para determinar asociaciones entre la variable principal y las variables secundarias del estudio y se calculó su área bajo la curva ROC (ABC). Del total de la muestra, 33 pacientes presentaron el alelo C del polimorfismo analizado (19,9%). El consumo de tabaco medio fue de 11.6 paquetes-año. El modelo multivariante arrojó los siguientes factores asociados al polimorfismo: mayor consumo tabáquico, ser mujer y no tener obesidad abdominal. El ABC fue de 0,706. Se ha encontrado asociación entre un mayor consumo de tabaco a lo largo de los años y la presencia del alelo C del polimorfismo rs1414334 del gen HTR2C. Se necesitan trabajos que corroboren nuestros resultados.