The burden of perioperative hypertension/hypotension: A systematic review.

STUDY OBJECTIVE: Our goal is to review the outcomes of acute hypertensive/hypotensive episodes from articles published in the past 10 years that assessed the short- and long-term impact of acute hypertensive/hypotensive episodes in the perioperative setting. METHODS: We conducted a systematic peer review based upon PROSPERO and Cochrane Handbook protocols. The following study characteristics were collected: study type, author, year, population, sample size, their definition of acute hypertension, hypotension or other measures, and outcomes (probabilities, odds ratio, hazard ratio, and relative risk) and the p-values; and they were classified according to the type of surgery (cardiac and non-cardiac). RESULTS: A total of 3,680 articles were identified, and 66 articles fulfilled the criteria for data extraction. For the perioperative setting, the number of articles varies by outcome: 20 mortality, 16 renal outcomes, 6 stroke, 7 delirium and 34 other outcomes. Hypotension was reported to be associated with mortality (OR 1.02-20.826) as well as changes from the patient's baseline blood pressure (BP) (OR 1.02-1.36); hypotension also had a role in the development of acute kidney injury (AKI) (OR 1.03-14.11). Postsurgical delirium was found in relation with BP lability (OR 1.018-1.038) and intra- and postsurgical hypotension (OR 1.05-1.22), and hypertension (OR 1.44-2.34). Increased OR (37.67) of intracranial hemorrhage was associated to postsurgical systolic BP >130 mmHg. There was a wide range of additional diverse outcomes related to hypo-, hypertension and BP lability. CONCLUSIONS: The perioperative management of BP influences short- and long-term effects of surgical procedures in cardiac and non-cardiac interventions; these findings support the burden of BP fluctuations in this setting.

Off-label drug use in neonates and infants in Spain: A five-year observational study.

OBJECTIVES: To provide information about the off-label rate of all drug prescriptions in neonates and infants up to 1 year in Spain. Also, to analyse the off-label prescription of medicines under current practice in this age group according to different evidence sources. STUDY DESIGN: A five-year (2015-2019) exploratory observational study about off-label prescription in neonates and infants (0 to 1 year) at primary health care in Spain. All drug prescriptions in this age group were analysed and classified according to their labelling in off-label or on-label. The drugs prescribed off-label were subsequently reviewed in national formularies and other databases to assess its evidence of use beyond what is recommended in the Summary of Product Characteristics (SmPC). RESULTS: On average 34.50% of total prescriptions were prescribed off-label according to the SmPC. 17.93% of total prescriptions in neonates and infants up to 1 year old were not based on clinical evidence from SmPC, Pediamécum, BNF or DailyMed. In more than 88% of cases, off-label use was related to the posology section of the SmPC, followed by the therapeutic indications and contraindications sections, in 35.20% and 24.10% of cases, respectively. Almost 13% of off-label drugs were over-the-counter. Salbutamol followed by topical tobramycin and colecalciferol were the drugs most prescribed off-label. CONCLUSIONS: Off-label use of drugs remains as an important public health concern, especially for neonates and infants up to 1 year, who receive the greatest proportion of off-label prescriptions. The evidence-based off-label prescription is a widespread practice that has shown a stable trend during the 5-year study period providing also a certain extent of flexibility to paediatricians in some therapeutic decisions.

Uso fuera de indicación de la combinación a dosis fija de tramadol/dexketoprofeno en atención primaria de salud: ¿Basado en la evidencia científica o motivo de preocupación? / Off-label use of fixed-dose combination of tramadol and dexketoprofen in primary health care. Evidence-based or cause for concern?

Introducción: La utilización de la combinación a dosis fija de tramadol/dexketoprofeno en España y en otros países ha aumentado de forma conside-rable. La indicación terapéutica autorizada de este medicamento es el tratamiento sintomático a corto plazo del dolor agudo de moderado a intenso en pacientes adultos. El objetivo de este estudio fue describir el patrón de uso de tramadol/dexketopro-feno en el ámbito de la atención primaria de salud.Método: Se realizó un estudio transversal, descrip-tivo y multicéntrico. La población de estudio incluyó a todos los pacientes de una Dirección de Atención Primaria (53 equipos de Atención Primaria) que tenían activa la prescripción de tramadol/dexke-toprofeno el 28 de marzo de 2018. La población diana fueron aquellos pacientes a los que se les prescribió tramadol/dexketoprofeno durante más de 20 días.Resultados: Un total de 176 pacientes tenía activa la prescripción de tramadol/dexketoprofeno. Todos los pacientes (100%) tuvieron una duración del tratamiento superior a 5 días y el 72,7% (N=128) su-perior a 20 días. La duración media del tratamiento fue de 14±160,9 días en pacientes que tenían me-nos de 20 días de tratamiento y de 224±160,8 días en pacientes que tenían más de 20 días de trata-miento. El 35,1% de los pacientes estaban tratados con más de 2 medicamentos para aliviar el dolor de forma concomitante con tramadol/dexketoprofeno. El médico de atención primaria inició un 65,6% de las prescripciones.Conclusiones: La combinación a dosis fija de tramadol/dexketoprofeno se utilizó con frecuencia fuera de indicación, de acuerdo con la ficha técnica y la evidencia científica disponible. Este estudio alerta sobre los riesgos potenciales asociados a la utilización de este medicamento en la práctica clíni-ca, como son la falta de efectividad y/o la aparición de efectos adversos. (AU)

Introduction: The use of the fixed-dose combi-nation of tramadol/dexketoprofen in Spain and in other countries has increased considerably. The authorized therapeutic indication for this medicinal product is the short-term symptomatic treatment of moderate to severe acute pain in adult patients. The objective of this study was to describe the pat-tern of use of tramadol/dexketoprofen in the field of primary health care.Method: A cross-sectional, descriptive and mul-ticenter study was carried out. The study popu-lation included all patients from a Primary Care Department (53 Primary Care teams) with an active prescription of tramadol/dexketoprofen on March 28, 2018. The target population was those patients who were prescribed tramadol/dexketoprofen. dexketoprofen for >20 days.Results: A total of 176 patients had an active pre-scription for tramadol/dexketoprofen. All patients (100%) had a duration of treatment greater than 5 days and 72.7% (N=128) greater than 20 days. The mean duration of treatment was 14±160.9 days in patients who had less than 20 days of treatment and 224±160.8 days in patients who had more than 20 days of treatment. 35.1% of the patients were treated with >2 pain medications and concomi-tantly with tramadol/dexketoprofen. The general practitioner initiated 65.6% of the prescriptions.Conclusions: The fixed-dose combination of tra-madol/dexketoprofen was frequently used off-la-bel, according to the product characteristics and the available scientific evidence. This study warns about the potential risks associated with the use of this drug in clinical practice, such as lack of effec-tiveness and/or the appearance of adverse effects (AU)

Indirect costs associated with skin infectious disease in children: a systematic review.

BACKGROUND: There are limited data in the literature on the indirect costs associated with skin and soft tissue infections (SSTIs) in the pediatric population. This study aimed to conduct a systematic review of the indirect costs associated with SSTIs in children. METHODS: The search was conducted in PubMed, SCOPUS, and Web of Science up to January 2020. Thirteen search strategies were designed combining MeSH terms and free terms. SSTIs were defined as bacterial or viral infections, dermatomycoses, and parasitic infestations. Only primary studies were included. All analyzed costs were converted to 2020 Euros. RESULTS: Thirteen of the identified publications presented indirect costs of SSTIs in children and were conducted in Argentina, Australia, Brazil, Hungary, New Zealand, Poland, Spain, Taiwan, and the USA. Nine studies described indirect costs associated with infection of Varicella-zoster virus: lost workdays by outpatient caregivers ranged from 0.27 to 7.8, and up to 6.14 if caring for inpatients; total productivity losses ranged from €1.16 to €257.46 per patient. Three studies reported indirect costs associated with acute bacterial SSTIs (community-associated methicillin-resistant Staphylococcus aureus) in children: total productivity losses ranged from €1,814.39 to €8,224.06 per patient, based on impetigo, cellulitis, and folliculitis. One study of parasitic infestations (Pediculus humanus capitis) reported total indirect costs per patient of €68.57 (formal care) plus €21.41 due to time lost by parents in purchasing treatment. CONCLUSIONS: The economic burden of SSTIs is highly relevant but underestimated due to the lack of studies reporting indirect costs. Further cost studies will allow a better understanding of the magnitude of the financial burden of the disease.

Tapentadol and Oxycodone/Naloxone Prescribing Patterns in Primary Health Care in Catalonia, Spain: A Cross-Sectional Study.

OBJECTIVE: To characterize the use of tapentadol and the combination oxycodone/naloxone in primary health care. Data on their use and possible misuse will allow the identification of risk factors and to design protocols to reduce and prevent avoidable harm to patients being treated for pain. DESIGN: A descriptive, cross-sectional and multicenter study was performed. SETTING: Fifty-three primary health care teams, which provides healthcare for 1,300,000 inhabitants. PATIENTS: A total of 1840 patients had active prescriptions of tapentadol and 985 of oxycodone/naloxone. METHODS: Demographic (age, sex) and clinical (glomerular filtration rate; active liver disease; dosing and duration of treatment), prescribed daily dose (according to age, sex, length of treatment), concomitant analgesic treatment and diagnosis. Patient information was obtained from medical records. RESULTS: Most of the patients were women (>74.0% in both cases), and the average age was 69.3 years (women: 70.1±13.2; men: 66.7±13.9 years) in the case of tapentadol and 70.6 years (women: 64.0±13.6; men: 72.6±14.3 years) in the case of oxycodone/naloxone. Only 12.2% of patients taking tapentadol and 12.1% taking oxycodone/naloxone had a normal renal function. In both cases, 4.1% of patients had active liver disease. The average length of treatment was 246.4 days in oxycodone/naloxone and 199.0 days in tapentadol. It was recorded that 85.1% of patients in the case of tapentadol and 89.0% in the oxycodone/naloxone had at least another drug prescribed for pain. About 42.2% of patients treated with tapentadol and 34.4% of patients treated with oxycodone/naloxone had associated neuralgia as a diagnosis. CONCLUSION: The pattern of use and profile of patients with tapentadol and oxycodone/naloxone had more similarities than differences, and suggested that prescribing practice, and monitoring should be assessed regularly to ensure patient safety and effective management of pain.

Gluten in pharmaceutical products: a scoping review.

BACKGROUND: Celiac disease (CD) is one of the most common gluten-related disorders. Although the only effective treatment is a strict gluten-free diet, doubts remain as to whether healthcare professionals take this restriction into consideration when prescribing and dispensing medicines to susceptible patients. This scoping review aimed to find out the current evidence for initiatives that either describe the gluten content of medicines or intend to raise awareness about the risk of prescribing and dispensing gluten-containing medicines in patients with CD and other gluten-related disorders. METHODS: A scoping review was conducted using three search strategies in PubMed/MEDLINE, TripDatabase and Web of Science in April 2021, following the PRISMA extension for scoping reviews (PRISMA-ScR). References from included articles were also examined. Two researchers screened the articles and results were classified according to their main characteristics and outcomes, which were grouped according to the PCC (Population, Concept and Context) framework. The initiatives described were classified into three targeted processes related to gluten-containing medicines: prescription, dispensation and both prescription and dispensation. RESULTS: We identified a total of 3146 records. After the elimination of duplicates, 3062 articles remained and ultimately 13 full texts were included in the narrative synthesis. Most studies were conducted in the US, followed by Canada and Australia, which each published one article. Most strategies were focused on increasing health professional's knowledge of gluten-containing/gluten-free medications (n = 8), which were basically based on database development from manufacturer data. A wide variability between countries on provided information and labelling of gluten-containing medicines was found. CONCLUSION: Initiatives regarding the presence of gluten in medicines, including, among others, support for prescribers, the definition of the role of pharmacists, and patients' adherence problems due to incomplete labelling of the medicines, have been continuously developed and adapted to the different needs of patients. However, information is still scarce, and some aspects have not yet been considered, such as effectiveness for the practical use of solutions to support healthcare professionals.

Effects of the Off-Label Drug Prescription in the Paediatric Population in Spain from the Adoption of the Latest European Regulation: A Pre-Post Study.

The year 2021 marks the 15th anniversary of the Paediatric Regulation (1901/2006/EC) in Europe. The main aim of the study was to conduct a pre-post comparison on the annual off-label prescription rates in the under-18 population in Spain and assess the potential influence of the Paediatric Regulation adoption. An observational study in the paediatric population was performed. Four cross-sectional annual periods, one before and the three latest periods after the adoption of the Regulation, were compared. Prescriptions in the primary health care setting were sorted by age group and drug and off-label status were determined. The number of off-label prescriptions issued by paediatricians was over two million per year. Prior to the adoption of the Paediatric Regulation, the off-label prescription rate was estimated at 7% of total prescriptions. Although the increase in the off-label rate over the study periods was mild, it was statistically significant (OR: 1.045; 95% CI: 1.043-1.046; p < 0.05). One of the most vulnerable population groups was neonates and infants up to 1 year, in which the off-label prescription rates showed the highest increase during the post follow-up period, which was statistically significant (OR: 4.270; 95% CI: 4.253-4.287; p < 0.05). The findings can help raise awareness and advocate for the development and authorization of medicines for children in the primary health care setting.

Analysis of the Financial Impact of Using Cangrelor on the Safety and Efficacy Outcomes in Patients Undergoing Percutaneous Coronary Intervention in Whom Oral Therapy with P2Y12 Inhibitors is Not Feasible or Desirable, in Spain.

PURPOSE: Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor indicated for the reduction of thrombotic cardiovascular events in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) in whom oral P2Y12 inhibitors are not feasible or desirable. The objective was to assess the financial impact of introducing cangrelor into the hospital formulary in Spain. PATIENTS AND METHODS: A budget impact model was developed to calculate the cost difference between two scenarios (without and with cangrelor) to treat CAD patients undergoing PCI in whom oral P2Y12 inhibitors are not feasible or desirable, over 3 years. Intravenous P2Y12 inhibitor (cangrelor), oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor), and glycoprotein IIb-IIIa inhibitors (GPIs) for bail-out use were considered. Epidemiological, efficacy (thrombotic events including cardiac death), safety (bleeding events), and costs (€, 2019) data were based on Spanish registries, clinical trials, and meta-analyses. One-way sensitivity analysis established the effect of uncertainty on results. RESULTS: For years 1, 2, and 3, the target population to receive cangrelor was 607, 1,822, and 3,340 patients, and cangrelor uptake was 23.70%, 58.30%, and 51.30%, respectively. The 3-year budget impact was 1,021,717€ varying from 50,245€ in year 1 to 599,272€ in year 3. The results were sensitive to the number of patients treated with GPIs in Spanish hospitals. CONCLUSION: Based on our results, the financial effort needed to introduce the use of cangrelor in patients undergoing PCI in whom antiplatelet therapy with oral P2Y12 inhibitors is not feasible or desirable barely exceeds one million € over three years, in Spain.

Prevention strategies to identify LASA errors: building and sustaining a culture of patient safety.

BACKGROUND: Potential look-alike, sound-alike (LASA) errors in outpatient and inpatient prescriptions have been widely described worldwide. However, most strategies of reducing drug name confusion have been only focused on the processes of prescribing and dispensing, often following local rules. MAIN TEXT: An illustrative recent example about this topic is given: the antidepressant Brintellix® (vortioxetine) (Takeda Pharmaceuticals USA, Inc.) and the antiplatelet medication Brilinta® (ticagrelor) (AstraZeneca LP). Revision of the initiatives that are currently applied to prevent potential LASA errors in different countries around the world and debate about the emerging strategies that could be implemented in short and mid-term. At present, a common policy worldwide on the authorization of unique names for innovative medicines does not exist. The implication of authorities in topdown strategies and the importance of developing an international health policy on the authorization of unique names for innovative medicines are highlighted in the following piece of opinion. CONCLUSIONS: Building and sustaining a culture of patient safety should be considered as a global top-down strategy which involved all the elements in the system (regulatory bodies, manufacturers and suppliers). The precedent established by the FDA in prevention strategies to identify and avoid LASA errors has been extremely important and should lead to international discussion. Coordinated international efforts are urgently needed in this area for the sake of patients' safety.

Clinical Use of Pregabalin in General Practice in Catalonia, Spain: A Population-Based Cross-Sectional Study.

Objective: The aim of this study was to determine the pattern of use of pregabalin and the appropriateness of treatment, so that interventions could be designed to improve various clinical approaches to the use of pregabalin to include unlicensed indications. Design: A descriptive, cross-sectional, multicenter study was performed between April 2014 and January 2015. Setting: Fifty-three primary health care centers covering 1,250,000 inhabitants. Subjects: A total of 10,155 patients with pregabalin prescriptions. Methods: Demographic (gender, age) and clinical (licensed indications for pregabalin, treatment duration, dosing schedule, diagnoses, kidney function, previous treatment with pregabalin, and additional drug treatment combined with pregabalin) variables obtained from health records were studied. The indicators were related to the daily dose of pregabalin, diagnoses, and treatment. Results: A total of 64.2% of patients treated with pregabalin were female (mean age = 62.3 years; SD = 15.2 years). Twenty-nine patients were younger than age 18 years. A total of 68.2% of patients were taking pregabalin for an appropriate indication, 45.2% were using pregabalin off-label for bone and joint pain, and 15.1% were using pregabalin for fibromyalgia. A total of 71.9% of patients started treatment with pregabalin without previously using firstline drugs, such as amitriptyline or gabapentin, and 66% of active treatments had been initiated during the year before the study. In 47% of patients with glomerular filtration rates lower than 15 mL/min, the dose exceeded the maximum. Conclusions: Our study reveals that pregabalin is used for unlicensed indications and often when firstline drugs have not been trialed and suggests that better routines in diagnosis and prescription may improve treatment outcomes. Our study also provides novel information about the use of doses of pregabalin that are higher than recommended for patients with renal impairment.

El coste económico de los procedimientos de contención mecánica de origen psiquiátrico en España / The economic cost of psychiatric mechanical restraint in Spain

La agitación de origen psiquiátrico ocurre principalmente en pacientes con trastornos psicóticos como la esquizofrenia, el trastorno esquizoafectivo y la fase maníaca del trastorno bipolar. Los métodos tradicionales para el control de los pacientes agitados incluyen la contención verbal, la contención farmacológica y la contención mecánica. En este estudio se ha estimado el coste directo sanitario asociado a la aplicación de las técnicas de contención mecánica de origen psiquiátrico en España. La cuantificación se realizó en función del tiempo empleado por profesional o número de visitas. La valoración de los recursos se realizó a partir de costes unitarios y datos epidemiológicos publicados. La aplicación de un procedimiento de contención mecánica a un paciente psiquiátrico supone un coste total por episodio de 513-1.160 Euros (considerando una duración de 4 a 12 h, respectivamente). El coste total anual se ha estimado en 27 millones de euros, considerando una duración por episodio de 4 h (AU)

Agitation is a group of psychiatric symptoms that commonly occur in patients with psychotic disorders, including schizophrenia, schizoaffective disorder and manic phase of bipolar disorder. Traditional methods of controlling agitated patients include verbal de-escalation, mechanical and pharmacological restraints. This study attempts to determine the direct medical costs attributable to psychiatric mechanical restraint in Spain. This resource was evaluated using published unit costs and national epidemiological data. The estimated direct costs of a restraint episode ranged from Euros 513-Euros 1,160 (4 -12 h per episode duration, respectively). Total annual costs of psychiatric mechanical restraint considering a duration of 4 h per episode were estimated at Euros 27 million (AU)

Evaluation of electronic prescription implementation in polymedicated users of Catalonia, Spain: a population-based longitudinal study.

OBJECTIVES: To assess whether electronic prescribing is a comprehensive health management tool that may contribute to rational drug use, particularly in polymedicated patients receiving 16 or more medications in the public healthcare system in the Barcelona Health Region (BHR). DESIGN: 16 months of retrospective study followed by 12 months of prospective monitoring. SETTING: Primary healthcare in BHR, Catalonia, Spain. PARTICIPANTS: All insured patients, especially those who are polymedicated in six basic health areas (BHA). Polymedicated patients were those with a consumption of ≥16 drugs/month. INTERVENTIONS: Monitoring demographic and consumption variables obtained from the records of prescriptions dispensed in pharmacies and charged to the public health system, as well as the resulting drug use indicators. Territorial variables related to implementation of electronic prescribing were also described and were obtained from the institutional data related to the deployment of the project. MAIN OUTCOME MEASURES: Trend in drug use indicators (number of prescriptions per polymedicated user, total cost per polymedicated user and total cost per prescription) according to e-prescription implementation. RESULTS: There was a significant upward trend in the number of polymedicated users, number of prescriptions and total cost (p<0.05), which seemed independent from the implementation of electronic prescribing when comparing the preimplementation and postimplementation period. Prescriptions per user and cost per user showed a decrease between the preimplementation and postimplementation period, being significant in two BHAs (p<0.05). CONCLUSIONS: Results suggest that after the implementation of electronic prescribing, the rationality of prescribing in polymedicated patients improved. In addition, this study provides a very valuable approach for future impact assessment.

Profile, cost and pattern of prescriptions for polymedicated patients in Catalonia, Spain.

OBJECTIVES: Polypharmacy is one of the main management issues in public health policies because of its financial impact and the increasing number of people involved. The polymedicated population according to their demographic and therapeutic profile and the cost for the public healthcare system were characterised. DESIGN: Cross-sectional study. SETTING: Primary healthcare in Barcelona Health Region, Catalonia, Spain (5 105 551 inhabitants registered). PARTICIPANTS: All insured polymedicated patients. Polymedicated patients were those with a consumption of ≥16 drugs/month. MAIN OUTCOMES MEASURES: The study variables were related to age, gender and medication intake obtained from the 2008 census and records of prescriptions dispensed in pharmacies and charged to the public health system. RESULTS: There were 36 880 polymedicated patients (women: 64.2%; average age: 74.5±10.9 years). The total number of prescriptions billed in 2008 was 2 266 830 (2 272 920 total package units). The most polymedicated group (up to 40% of the total prescriptions) was patients between 75 and 84 years old. The average number of prescriptions billed monthly per patient was 32±2, with an average cost of €452.7±27.5. The total cost of those prescriptions corresponded to 2% of the drug expenditure in Catalonia. The groups N, C, A, R and M represented 71.4% of the total number of drug package units dispensed to polymedicated patients. Great variability was found between the medication profiles of men and women, and between age groups; greater discrepancies were found in paediatric patients (5-14 years) and the elderly (≥65 years). CONCLUSIONS: This study provides essential information to take steps towards rational drug use and a structured approach in the polymedicated population in primary healthcare.