Prevalence, country-specific prescribing patterns and determinants of benzodiazepine use in community-residing older adults in 7 European countries.

BACKGROUND: The use of benzodiazepines (BZDs) in older population is often accompanied by drug-related complications. Inappropriate BZD use significantly alters older adults' clinical and functional status. This study compares the prevalence, prescribing patterns and factors associated with BZD use in community-dwelling older patients in 7 European countries. METHODS: International, cross-sectional study was conducted in community-dwelling older adults (65 +) in the Czech Republic, Serbia, Estonia, Bulgaria, Croatia, Turkey, and Spain between Feb2019 and Mar2020. Structured and standardized questionnaire based on interRAI assessment scales was applied. Logistic regression was used to evaluate factors associated with BZD use. RESULTS: Out of 2,865 older patients (mean age 73.2 years ± 6.8, 61.2% women) 14.9% were BZD users. The highest prevalence of BZD use was identified in Croatia (35.5%), Spain (33.5%) and Serbia (31.3%). The most frequently prescribed BZDs were diazepam (27.9% of 426 BZD users), alprazolam (23.7%), bromazepam (22.8%) and lorazepam (16.7%). Independent factors associated with BZD use were female gender (OR 1.58, 95%CI 1.19-2.10), hyperpolypharmacy (OR 1.97, 95%CI 1.22-3.16), anxiety (OR 4.26, 95%CI 2.86-6.38), sleeping problems (OR 4.47, 95%CI 3.38-5.92), depression (OR 1.95, 95%CI 1.29-2.95), repetitive anxious complaints (OR 1.77, 95%CI 1.29-2.42), problems with syncope (OR 1.78, 95%CI 1.03-3.06), and loss of appetite (OR 0.60, 95%CI 0.38-0.94). In comparison to Croatia, residing in other countries was associated with lower odds of BZD use (ORs varied from 0.49 (95%CI 0.32-0.75) in Spain to 0.01 (95%CI 0.00-0.03) in Turkey), excluding Serbia (OR 1.11, 95%CI 0.79-1.56). CONCLUSIONS: Despite well-known negative effects, BZDs are still frequently prescribed in older outpatient population in European countries. Principles of safer geriatric prescribing and effective deprescribing strategies should be individually applied in older BZD users.

Geographical distribution of clinical trials in amyotrophic lateral sclerosis: a scoping review.

Introduction: Clinical trials location is determined by many factors, including the availability of patient populations, regulatory environment, scientific expertise, and cost considerations. In clinical drug development of amyotrophic lateral sclerosis (ALS), where genetic differences have been described and may be related to geographic setting, this could have implications for the clinical interpretation of results in underrepresented geographic settings. Objective: The aim of this study was to review country participation in ALS clinical research based on available data from clinical trial registries and databases. Methods: We performed a scoping review with available information about clinical trials on ALS in ClinicalTrials.gov (CT), EU clinical trials register (EudraCT), WHO International Clinical Trials Registry Platform (ICTRP) and Web of Science (WOS). Inclusion criteria were clinical trials in phase 2 and 3 to treat ALS, recruiting or active not recruiting, from 23/06/2018 to 23/06/2023. Results: The total number of clinical trials identified were 188; 54 studies in CT, 38 in EudraCT, 47 in ICTRP and 49 in WOS. We identified 77 clinical trials after deleting duplicates and applying exclusion criteria. The countries with most studies conducted were the US with 35 studies (10.9%), followed by the United Kingdom, Belgium, France and Germany with 21 studies each one of them (6.5%). Conclusion: The data obtained in our review showed a non-homogeneous distribution in clinical trials at the international level, which may influence the interpretation of the results obtained.

Drug-Related Problems Detected in Complex Chronic Patients by Community Pharmacists of Catalonia: Perception of the Person-Centred Approach Necessity.

Community pharmacies are healthcare settings in which pharmacists are in an ideal position to carry out pharmaceutical care. The aim of this study was to analyse the number, type and groups of drugs that caused drug-related problems (DRPs) detected in complex chronic patients who are outpatients, the interventions and actions of community pharmacists and their impact on patient medication adherence. The study was designed as a secondary analysis of a multicentre study in the field of primary healthcare and community pharmacies in Catalonia (Spain). The patients who took part were divided into two groups by the primary care physician depending on whether or not they were considered likely to receive their medication through a monitored dosage system (MDS) based on pre-established criteria. Patients underwent 12 months of follow-up by community pharmacists. The prevalence of DRPs among the studied complex chronic patients was high (n = 689). The most identified DRP was nonadherence (31.20%). In the MDS group, results showed a statistically significant increase of 21% in the number of adherent patients with respect to the baseline visit (p-value = 0.0008). Community pharmacists can have an important role in addressing DRPs and optimizing the safety and effectiveness of medications for these patients and in involving them in their own health conditions.

[Translated article] Design and validation of two instruments to analyze and evaluate the formal quality in the informed consent process of clinical trials with medicinal products.

OBJECTIVE: The activity of sponsors and Ethics Committees for Research with medicines has increased in recent years. The objective was to design and validate 2 instruments to analyze and evaluate the formal quality of the patient information sheet and the informed consent form of clinical trials with drugs, in accordance with the legislation. METHODS: Design (Guideline for good clinical practice and European and Spanish regulations); validation (Delphi method and expert consensus: concordance ≥ 80%); reliability (inter-observer method, Kappa index). 40 patient information sheets/informed consent forms were evaluated. RESULTS: Very good concordance was obtained in both checklists (k ≥ 0.81, p b 0.001). The final versions consisted of checklist-patient information sheet: 5 sections, 16 items and 46 sub-items; and checklist-informed consent form: 11 items. CONCLUSION: The instruments developed are valid, reliable and facilitate the analysis, evaluation, and decision-making on the patient information sheets/informed consent forms of clinical trials with drugs.

Design and validation of 2 instruments to analyze and evaluate the formal quality in the informed consent process of clinical trials with medicinal products. / Diseño y validación de 2 instrumentos para analizar y evaluar la calidad formal en el proceso de consentimiento informado de ensayos clínicos con medicamentos.

OBJECTIVE: The activity of sponsors and Ethics Committees for Research with medicines has increased in recent years. The objective was to design and validate 2 instruments to analyze and evaluate the formal quality of the patient information sheet and the informed consent form of clinical trials with drugs, in accordance with the legislation. METHOD: Design (Guideline for good clinical practice and European and Spanish regulations); validation (Delphi method and expert consensus: concordance ≥ 80%); reliability (inter-observer method, Kappa index). 40 patient information sheets/informed consent forms were evaluated. RESULTS: Very good concordance was obtained in both checklists (k ≥ 0.81, p < 0.001). The final versions consisted of checklist-patient information sheet: 5 sections, 16 items and 46 sub-items; and checklist-informed consent form: 11 items. CONCLUSION: The instruments developed are valid, reliable and facilitate the analysis, evaluation, and decision-making on the patient information sheets/informed consent forms of clinical trials with drugs.

Cross-cultural adaptation and validation of the Recognizing And Addressing Limited Pharmaceutical Literacy (RALPH) interview guide in community pharmacies.

BACKGROUND: The RALPH (Recognizing and Addressing Limited PHarmaceutical Literacy) interview guide makes it possible to identify patients with limited pharmaceutical knowledge and to assess their skills in the functional, communicative, and critical health literacy domains. OBJECTIVE: (s): To perform a cross-cultural validation of the RALPH interview guide in Spanish population; to conduct a descriptive analysis based on patients' responses. METHODS: A cross-sectional study of patients' pharmaceutical literacy skills was conducted in three stages: systematic translation, administration of the interview and analysis of psychometric properties. The target population included adult patients (≥18 years) who attend one of the participating community pharmacies in Barcelona (Spain). Content validity was evaluated by an expert committee. Viability was assessed in the pilot test, and reliability was assessed using internal consistency and intertemporal stability. Construct validity was assessed by factor analysis. RESULTS: A total of 103 patients were interviewed at 20 pharmacies. Cronbach's alpha values based on standardized items ranged between 0.720 and 0.764. For the longitudinal component, the ICC test-retest reliability was 0.924. The factor analysis was verified by KMO (0.619) and Bartlett's test of sphericity (P-value <0.05). The definitive RALPH guide translated into Spanish maintains the same structure as the original. Some expressions were simplified, and the questions on the comprehension of warnings or specific instructions for use, contradictory information and shared decision-making were reformulated. Pharmaceutical literacy skills were seen to be most limited with regard to the critical domain. The responses of the Spanish patients were in agreement with the original results of the RALPH interview guide. CONCLUSIONS: The RALPH interview guide in Spanish complies with the requirements viability, validity, and reliability. This tool may be able to identify the low pharmaceutical literacy skills of patients coming to community pharmacies in Spain, and its use may also be extended to other Spanish-speaking countries.

Person-centred care provided by a multidisciplinary primary care team to improve therapeutic adequacy in polymedicated elderly patients (PCMR): randomised controlled trial protocol.

INTRODUCTION: The increase in elderly population has led to an associated increase in multiple pathologies, frailty, polypharmacy, healthcare costs, decreased quality of life and mortality. We designed an intervention based on person-centred care model. This article outlines a study protocol, which aims to explore the effects of the intervention to improve therapeutic adequacy in polymedicated elderly patients. METHODS AND ANALYSIS: An open, randomised, multicentre, controlled clinical trial. The study population includes polymedicated (≥8 prescription medications) patients ≥75 years old. In the intervention group, the multidisciplinary team (primary care pharmacist, family doctor and nurse) will meet to carry out multidimensional reviews (frailty, clinical complexity, morbidity and therapeutic adequacy) of the study subjects. If changes are proposed to the treatment plan, a clinical interview will be conducted with the patient to agree on changes in accordance with their preferences. Follow-up visits will be scheduled at 6 and 12 months. In the control group, where the usual clinical practice will be followed, the necessary data will be collected to compare the results.The key variables are the variation in the mean number of incidents (potentially inappropriate prescription) per patient, the number of medications, the number of changes implemented to the treatment plan and the variation in the number of hospital admissions. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of the IDIAPJGol and by the University of Barcelona's Bioethics Commission. The results are expected to be published in peer reviewed open-access journals, and as part of a doctoral thesis. TRIAL REGISTRATION NUMBER: NCT04188470. Pre-results.

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.

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.

Development and Validation of the Hospital Outpatients' Information Needs Questionnaire (HOINQ).

PURPOSE: The main objective was to develop and validate a "Hospital Outpatients' Information Needs Questionnaire" (HOINQ). Secondly, to identify patients' preferred sources of information. Finally, to establish differences depending on the disease, as well as between sociodemographic and clinical variables. PATIENTS AND METHODS: This is a transversal study based on a questionnaire. All adult hospital outpatients' who collected their medication at the Pharmacy Service were consecutively recruited, regardless of their diagnosis time, treatment or disease. The Spanish version of the internationally validated European Organization for Research and Treatment Cancer Quality of Life Questionnaire (EORTC QLQ-25) aimed at oncology patients was used as the starting point. In order to be applicable on new target population, it was crucial to make several changes and ensure that it complies with the validity, viability and reliability criteria. The questionnaire prepared for validation was then obtained by a literature review (face validity), submitting the EORTC QLQ-25 to an expert committee (content validity), by piloting (viability) and Cronbach's alpha statistical analysis (reliability). Once the questionnaire was completed, Cronbach's alpha of the final study (reliability) and factor analysis (construct validity) were performed. Then, pertinent modifications were applied to obtain the HOINQ. RESULTS: A total of 153 outpatients filled the questionnaire, which was widely accepted and required 5-10 min to complete. Cronbach's alpha coefficients met criteria >0.7. Three factors were established by factor analysis: aspects about the disease, pharmacological and no-pharmacological treatment and satisfaction and perception of the information received. Participants felt satisfied (41-52%) with the information amount, quality and usefulness, although 1 out of 3 stated wanting to know more about the different information areas. Younger patients (P-value <0.05) and those who had been attending the Pharmacy Service for a longer time span (P-value <0.01) reported receiving more information. On a 0 to 7 scale, medical specialists (mean = 6.28, SD = 1.38) followed by the rest of health care professionals (mean = 4.23-4.63, SD = 2.25-2.29) were selected as the preferred sources of information. HIV patients reported being more informed, while those with rheumatoid arthritis felt less informed (P-value <0.05). CONCLUSION: The HOINQ was developed. It is a self-completed questionnaire, composed of three blocks: the 16-item information needs questionnaire, demographic and clinical variables, and patients' preferred sources of information. It is an easy tool to use and replicate, both for patients and professionals.

Effects of a multifaceted intervention in psychogeriatric patients: one-year prospective study.

OBJECTIVES: The aetiology of behavioural and psychological symptoms (BPSD) could be related to inadequate treatment in patients with dementia. The aim of this study was to determine how a multifaceted intervention based on a medication review and multidisciplinary follow-up could improve treatment and minimise risk in these patients. METHODS: A prospective interventional study was undertaken between July 2015 and July 2016 of patients with dementia admitted to control BPSD. Patients with previous psychiatric illness or palliative care were excluded. Prescription information was obtained from Aegerus and the Catalonia clinical record HC3. The intervention was conducted by a multidisciplinary team. The Medication Appropriateness Index (MAI) was used to assess the intervention. RESULTS: 65 patients (60% women, mean age 84.9±6.7 years) with mild-moderate cognitive impairment (mean 4.5±1.8), moderate-severe functional dependence (mean 43.8±23.9) and a high prevalence of geriatric syndromes and comorbidity were included in the study. 87.7% of the patients were taking ≥5 drugs (mean 9.0±3.1) and 38.5% were taking ≥10. Patients presented with BPSD values of 1.9±0.8 at admission. Common symptoms prompting admission were agitation (47.7%) and irritability (43.1%). A total of 175 drug-related problems (DRPs) were detected (2.97 per patient). Significant differences (p<0.001) were found between the MAI score at admission (4±4.6) and post-intervention (0.5±2.6). Most prevalent MAI criteria were related to interactions (40%), dosage (38.5%) and duplication (26.2%). 55 patients (84.6%) were taking anticholinergic drugs at admission (2.6±1.2 anticholinergic drugs per patient), and the post-intervention reduction was significant (p<0.016). CONCLUSIONS: The balance between effective treatment and safety is complex in these patients. Medication review in interdisciplinary teams is an essential component to optimise interventions and assessment of safety.

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.

Adverse Drug Events in Patients with Dementia and Neuropsychiatric/Behavioral, and Psychological Symptoms, a One-Year Prospective Study.

Older people usually present with adverse drug events (ADEs) with nonspecific symptoms such as cognitive decline, recurrent falls, reduced mobility, and/or major deterioration. The aims of this study were to assess the ADEs of patients with dementia and presenting neuropsychiatric/behavioral, and psychological symptoms in dementia (BPSD) and to categorize and identify the principal factors that allow to prevent ADEs, and separately ADEs that result in falls. To that end, a one-year prospective study in a psychogeriatric ward (July 2015 to July 2016) was performed. All patients admitted to this ward were eligible for enrolment. Patients who met any of the following criteria were excluded from the study: Patients without cognitive impairment, a length of stay under 7 days, and palliative or previous psychiatric pathology. We included 65 patients (60% women, 84.9 years ± 6.7) with mild to moderate cognitive impairment, moderate to severe functional dependence, and a high prevalence of geriatric syndromes and comorbidity. A total of 87.7% were taking five or more drugs (mean 9.0 ± 3.1). ADEs were identified during the interdisciplinary meeting and the follow up by clinical record. Sixty-eight ADEs (81.5% patients) were identified, of which 73.5% were not related to falls. From these, 80% were related to drugs of the nervous system. The Naranjo algorithm determined that 90% of ADEs were probable. The severity of the ADEs was Category E in 34 patients (68%). The number of preventable ADE according to the Schumork⁻Thornton test was 58%. The main ADE was drowsiness/somnolence (27.7%). ADEs related to falls represented a 26.5%. The balance between effective treatment and safety is complex in these patients. A medication review in interdisciplinary teams is an essential component to optimize safety prevention.

Readability assessment of package leaflets of biosimilars.

OBJECTIVES: To assess the degree of readability and the length of the package leaflets of biosimilars. SETTING: The package leaflets analysed were downloaded from the European Medicines Agency (EMA) website. PARTICIPANTS: The study sample included the package leaflets written in English of all the biosimilars that were authorised by the EMA on 31 August 2017, and whose content was available via the internet on that date (n=35). DESIGN: This was a cross-sectional analytical study. The readability of the package leaflets of all biosimilars authorised by the EMA in August 2017 was determined applying the Flesch and Flesch-Kincaid formulas. The influence of the following variables on the readability and length was also analysed: package leaflet section, type of biosimilar, date of first authorisation of the biosimilar and type of medicine. RESULTS: A considerable variation of the package leaflets length was found (3154±803). The readability of all the package leaflets overtook the recommended value for health-related written materials taking into account Flesch-Kincaid Index, and none of the package leaflets were easy to understand according to the Flesch Index. Statistically significant differences (p<0.05) were observed between the sections of package leaflets in readability indices and length. The most difficult sections to understand were those related with the therapeutic indication of medicine and the possible side effects. CONCLUSIONS: Package leaflets for authorised biosimilars may not fulfil the function for which they were designed. The competent organisations could be informed about the possible negative effect on the use of this type of medicines.

Current evidence in the stability of medicines in dose administration aids: implications for patient safety.

INTRODUCTION: As the elderly population and polypharmacy are increasing, it is predicted that interventions to enhance medication adherence, as dose administration aids (DAA), will grow. One of the limitations of repackaging medicines into DAA is to assure the stability of medicines, and, therefore, their quality, efficacy and safety. AREAS COVERED: This article collects and summarises data of all the stability studies of repackaged medicines into DAAs. Computerized search in databases: PubMed, Google Scholar, SciELO, and reference texts related to the field (keywords: drug stability, DAAs, compliance aids, and repackaging), open access databases and guidelines. Also, it provides recommendations on the suitability of repackaging and compares them with those established. EXPERT OPINION: Since medicines are removed from primary package, their stability can be compromised due to psychochemical characteristics of the drug substance and product, the dosage form, the type of DAA selected, the co-storage and splitting, the repackaging conditions, and the conditions of storage. This review reflects the need of more standardized stability studies to guarantee the quality of repackaged medicines. In addition, the importance of them to support the pharmacist to make the best decisions in order to maximize outcomes and minimize risks related to patients' medication when repackaging it.

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.

Sex-Divergent Clinical Outcomes and Precision Medicine: An Important New Role for Institutional Review Boards and Research Ethics Committees.

The efforts toward individualized medicine have constantly increased in an attempt to improve treatment options. These efforts have led to the development of small molecules which target specific molecular pathways involved in cancer progression. We have reviewed preclinical studies of sunitinib that incorporate sex as a covariate to explore possible sex-based differences in pharmacokinetics and drug-drug interactions (DDI) to attempt a relationship with published clinical outputs. We observed that covariate sex is lacking in most clinical outcome reports and suggest a series of ethic-based proposals to improve research activities and identify relevant different sex outcomes. We propose a deeper integration of preclinical, clinical, and translational research addressing statistical and clinical significance jointly; to embed specific sex-divergent endpoints to evaluate possible gender differences objectively during all stages of research; to pay greater attention to sex-divergent outcomes in polypharmacy scenarios, DDI and bioequivalence studies; the clear reporting of preclinical and clinical findings regarding sex-divergent outcomes; as well as to encourage the active role of scientists and the pharmaceutical industry to foster a new scientific culture through their research programs, practice, and participation in editorial boards and Institutional Ethics Review Boards (IRBs) and Research Ethics Committees (RECs). We establish the IRB/REC as the centerpiece for the implementation of these proposals. We suggest the expansion of its competence to follow up clinical trials to ensure that sex differences are addressed and recognized; to engage in data monitoring committees to improve clinical research cooperation and ethically address those potential clinical outcome differences between male and female patients to analyze their social and clinical implications in research and healthcare policies.

Provision of pharmaceutical care by community pharmacists across Europe: Is it developing and spreading?

RATIONALE, AIMS, AND OBJECTIVES: Pharmaceutical care involves patient-centred pharmacist activity to improve medicines management by patients. The implementation of this service in a comprehensive manner, however, requires considerable organisation and effort, and indeed, it is often not fully implemented in care settings. The main objective was to assess how pharmaceutical care provision within community pharmacy has evolved over time in Europe. METHOD: A cross-sectional questionnaire-based survey of community pharmacies, using a modified version of the Behavioural Pharmaceutical Care Scale (BPCS) was conducted in late 2012/early 2013 within 16 European countries and compared with an earlier assessment conducted in 2006. RESULTS: The provision of comprehensive pharmaceutical care has slightly improved in all European countries that participated in both editions of this survey (n = 8) with progress being made particularly in Denmark and Switzerland. Moreover, there was a wider country uptake, indicating spread of the concept. However, due to a number of limitations, the results should be interpreted with caution. Using combined data from participating countries, the provision of pharmaceutical care was positively correlated with the participation of the community pharmacists in patient-centred activities, routine use of pharmacy software with access to clinical data, participation in multidisciplinary team meetings, and having specialized education. CONCLUSIONS: The present study demonstrated a slight evolution in self-reported provision of pharmaceutical care by community pharmacists across Europe, as measured by the BPCS. The slow progress suggests a range of barriers, which are preventing pharmacists moving beyond traditional roles. Support from professional bodies and more patient-centred community pharmacy contracts, including remuneration for pharmaceutical care services, are likely to be required if quicker progress is to be made in the future.