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Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotic agents is associated with increased risks of both bleeding and thromboembolism. In this prospective intervention study, community pharmacists screened for NSAID-antithrombotic interactions and contacted the prescribing physician to discuss interaction management. We included 782 interactions; these were found in an older, polymedicated patient population (mean age: 68 y, median of 5 other drugs). Ibuprofen (in 43.0% of cases) and low-dose aspirin (78.8%) were the most frequently involved NSAID and antithrombotic, respectively. Anticoagulants were involved in 16.1% of interaction cases. For 61% of cases, the interacting drugs were prescribed by the same physician. The pharmacist-physician discussion about how to manage the interaction mostly resulted in no change of pharmacotherapy (60.7%); the most frequent reason given by physicians was that the NSAID was for short-term use only. In 39.3% of cases the discussion resulted in a pharmacotherapy change; replacing the NSAID by paracetamol was the most common change.

Continuous infusions of β-lactam antibiotics increase pharmacokinetic/pharmacodynamic target attainment. However, this way of administration brings about some practical issues such as stability. This study aims to determine the stability of a 90 mg/mL cefuroxime sodium solution. Cefuroxime sodium was reconstituted and mixed with 50-mL 0.9% saline to produce 90 mg/mL solution in polypropylene syringes which were stored at 4 °C, 25 °C and 40 °C. Cefuroxime sodium concentration was determined periodically over 14 days using a stability-indicating high-performance liquid chromatographic method with ultra-violet detection. The loss in concentration was less than 10% after 2 days of storage at 25 °C and less than 5% after 14 days of storage at 4 °C. The concentration fell below 60% after 1 day at 40 °C. Solutions darken in appearance with time and heat. A 90 mg/mL cefuroxime sodium solution stored in polypropylene syringes is stable for 2 days at 25 °C and for at least 14 days at 4 °C.

The concept of asthma inflammatory phenotypes has proved to be important in predicting response to inhaled corticosteroids. Induced sputum, which has been pivotal in the development of the concept of inflammatory phenotypes, is however not widely available. Several studies have proposed to use surrogate exhaled or blood biomarkers, like fractional exhaled nitric oxide (FENO), blood eosinophils and total serum immunoglobulin E (IgE). However, taken alone, each of these biomarkers has moderate accuracy to identify sputum eosinophilia. Here, we propose a new approach based on the likelihood ratio to study which thresholds of these biomarkers, taken alone or in combination, were able to rule in or rule out sputum eosinophils ≥3%. We showed in a large population of 869 asthmatics that combining FENO, blood eosinophils and total serum IgE could accurately predict sputum eosinophils ≥ or

Patients with headache often self-treat their condition with over-the-counter analgesics. However, overuse of analgesics can cause medication-overuse headache. The present study aimed to identify subgroups of individuals with headache who self-medicate, as this could be helpful to tailor intervention strategies for prevention of medication-overuse headache. Patients (n = 1021) were recruited from 202 community pharmacies and completed a self-administered questionnaire. A hierarchical cluster analysis was used to group patients as a function of sociodemographics, pain, disability, and medication use for pain. Three patient clusters were identified. Cluster 1 (n = 498, 48.8%) consisted of relatively young individuals, and most of them suffered from migraine. They reported the least number of other pain complaints and the lowest prevalence of medication overuse (MO; 16%). Cluster 2 (n = 301, 29.5%) included older persons with mainly non-migraine headache, a low disability, and on average pain in 2 other locations. Prevalence of MO was 40%. Cluster 3 (n = 222, 21.7%) mostly consisted of patients with migraine who also report pain in many other locations. These patients reported a high disability and a severe limitation of activities. They also showed the highest rates of MO (73%).

Background: Drug shortages represent a complex global problem affect-ing patients and health care professionals on a daily basis. Objectives: To identify, describe, and compare drug shortages in health care facilities in Canada and 4 European countries in early 2018. Methods: A descriptive cross-sectional study was conducted in 1 hospital in each of 5 countries: Canada, France, Belgium, Spain, and Switzerland. Over a 4-week period, shortage data were collected daily by each hospital using a standardized grid and a standard process. Results: From January 8 to February 2, 2018, there were a total of 84 shortages (median duration 32 days) in the Canadian hospital, 62 shortages (median duration 9 days) in the French hospital, 46 shortages (median duration 37 days) in the Belgian hospital, 28 shortages (median duration 25 days) in the Spanish hospital, and 98 shortages (median duration 68 days) in the Swiss hospital. The number of manufacturers implicated in the shortages was 28 for the Canadian hospital, 30 for the French hospital, 19 for the Belgian hospital, 16 for the Spanish hospital, and 42 for the Swiss hospital. Most of the shortages involved parenteral drugs, with both innovative and generic manufacturers being affected. Most therapeutic classes were affected by shortages to some extent, with the top 3 classes being anti-infective agents (accounting for 21.1% of shortages overall), central nervous system drugs (11.3%), and cardio-vascular drugs (8.2%). Conclusions: Drug shortages occurred almost daily in all of the study hospitals. Across the 5 hospitals, the frequency of shortages varied by a factor of 3, which may imply similar variability at the national level. All stakeholders should work more diligently to prevent and manage drug shortages. RESUME Contexte : Les penuries de medicaments representent un probleme mondial complexe qui touche quotidiennement les patients et les professionnels de la sante. Objectifs : Recenser, decrire et comparer les penuries de medicaments ayant eu lieu au debut de 2018 dans des etablissements de soins de sante du Canada et de quatre pays d’Europe. Methodes : Une etude descriptive et transversale a ete menee dans un hopital de chacun des cinq pays suivants : le Canada, la France, la Belgique, l’Espagne et la Suisse. Sur une periode de quatre semaines, chaque hopital a recueilli quotidiennement les donnees sur les penuries a l’aide d’une grille et d’un processus normalises. Resultats : Pour la periode allant du 8 janvier au 2 fevrier 2018, on a recense 84 penuries (duree mediane de 32 jours) dans l’hopital canadien, 62 penuries (duree mediane de 9 jours) dans l’hopital francais, 46 penuries (duree mediane de 37 jours) dans l’hopital belge, 28 penuries (duree mediane de 25 jours) dans l’hopital espagnol et 98 penuries (duree mediane de 68 jours) dans l’hopital suisse. Vingt-huit (28) fabricants etaient impliques dans les cas de penuries dans l’hopital canadien, 30 dans l’hopital francais, 19 dans l’hopital belge, 16 dans l’hopital espagnol et 42 dans l’hopital suisse. La plupart des penuries touchaient les medicaments parenteraux et mettaient en cause tant les fabricants de medicaments novateurs que ceux de medicaments generiques. Les penuries ont affecte d’une maniere ou d’une autre la plupart des classes de medicaments , mais les trois classes les plus touchees etaient les agents anti-infectieux (21,1 %) les medicaments agissant sur le systeme nerveux central (11,3 %) et les agents cardiovasculaires (8,2 %). Conclusions : Des penuries survenaient presque quotidiennement dans chaque hopital de l’etude. Dans l’ensemble des hopitaux, la frequence des penuries variait selon un facteur de trois, ce qui pourrait se traduire par une variabilite semblable a l’echelle nationale. Toutes les parties prenantes doivent travailler avec plus d’ardeur a la prevention et a la gestion des penuries de medicaments.

Pain is a common reason for self-medication with over-the-counter (OTC) analgesics. However, this self-treating population has remained largely uncharacterized. This cross-sectional observational study investigated individuals who self-medicate their pain with OTC analgesics to elucidate their pain characteristics and medication use. In addition, presence of and risk factors for concerns about pain medication were examined. The clinical profile of the participants (n = 1,889) was worse than expected with long-standing pain complaints (median pain duration of 9 years), pain located at multiple body sites (median of 4, and 13% with ≥10 painful body areas), about one-third suffering from daily pain and about 40% experiencing substantial pain-related disability. Head (58.6% of sample), low back (43.6%), and neck (30.7%) were the most common pain locations. About 73% had a physician diagnosis, mainly migraine and osteoarthritis. Paracetamol (used by 68.6% of patients) and nonsteroidal anti-inflammatory drugs (46.8%) were the most frequently used pain medications. About 40% of our sample showed substantial concern about the perceived need for pain medication and the perceived potential for harmful effects (eg, fear for addiction). These findings highlight the importance for health professionals to systematically probe pain patients about their self-medication practices and explore attitudes about pain medication. Perspective: This study found that the clinical picture of people who self-medicate their pain with OTC analgesics looked worse than expected. We also identified substantial concerns about pain medication. Therefore, we recommend that health professionals systematically probe pain patients about their self-medication practices and explore concerns about pain medication.

Background: The main objectives of this study were to evaluate the use of antibiotics; assess the knowledge and perception of prescribers regarding the use of antibiotics; to describe the policy on the use of antibiotics and to identify factors associated with high antibiotic consumption at the University Hospital of Conakry. Methods: This study has two components: a retrospective study covering three months' consumption of antibiotics (From January 2013 to March 2013), and a cross-sectional study on both the knowledge and perception of prescribers concerning the use of antibiotics and the policies on their proper use. Results: Of a total of 1,199 cases examined at the University Hospital of Conakry, 953 patients received at least one antibiotic about 79.5% of the total cases. The total amount consumed was 55.3 DDD / 100 BD. The class of the Extended-spectrum penicillin’s was widely the most used at 22.9 DDD / 100 BD. The median knowledge score of prescribers; valued at a total of 8, was equal to 5. The Composite Index for proper use of Antibiotic (CIATB) was 2.25 / 20. Determinants or factors associated with the large use of antibiotics were the hospital site, the ward and the average length of stay. Conclusion: Based on the results of our study, it appears that lot antibiotics are largely consumed at the University Hospital of Conakry; and that consumption are influenced by the hospital site, the ward and the length of stay. This study reveals also the absence of any policy of the rational use of antibiotics. Therefore, the study illustrates the need for the implementation of an antimicrobial stewardship action.

Older adults often resort to self-medication to relieve symptoms of their current illnesses; however, the risks of this practice are multiplied in old age. In particular, this age group is more vulnerable to adverse drug events because of the physiological changes that occur due to senescence. The aim of the study was to obtain an overview of the adverse health events related to self-medication among subjects aged 60 years and over through a systematic review of the literature. A study of relevant articles was conducted among databases (MEDLINE, PsycINFO, and EBM Reviews–Cochrane Database of Systematic Reviews). Eligibility criteria were established and applied by two investigators to include suitable studies. The results and outcomes of interest were detailed in a descriptive report. The electronic search identified 4096 references, and the full texts of 74 were reviewed, of which four were retained in the analysis: three had a cross-sectional design and one prospectively followed elderly subjects. The first study showed a 26.7% prevalence of adverse drug reactions (ADRs) among elders, the second study found a 75% prevalence of side effects, and, finally, a prospective study showed an ADR incidence of 4.5% among self-medicated elders. These studies showed that adverse health events related to self-medication are relatively frequently reported. They also highlighted that analgesics and anti-inflammatory drugs are the most self-medicated products, while vitamins and dietary supplements also appear to be frequently self-administered, but by older individuals. Studies on self-medication in the elderly and its adverse health effects are clearly lacking. There is a need to perform prospective studies on this topic to gain a clear understanding of the extent of this problem and to enhance the awareness of health professionals to better inform seniors.

Background Patients with rhinitis often self-medicate with over-the-counter drugs, however this self-treating population has remained largely unstudied. Objective To characterize individuals self-medicating persistent rhinitis and to determine the prevalence of and risk factors for intranasal decongestant overuse within this population. Methods A cross-sectional observational study of individuals self-medicating persistent rhinitis (defined according to the Allergic Rhinitis and its Impact on Asthma guidelines). Participants (n = 895) completed a self-administered questionnaire to assess current symptoms, rhinitis medication, and previous physician diagnosis. Intranasal decongestant overuse was defined as daily use for at least 1 year. Results The vast majority of subjects (95%) had moderate-to-severe rhinitis. Nasal congestion was the predominant symptom (median visual analog scale, 6.6 cm; interquartile range, 3.4 cm). Sixty-five percent had had their current nasal problems for more than 5 years. Approximately 80% had a physician diagnosis (mainly allergic rhinitis or rhinosinusitis). The prevalence of intranasal decongestant overuse was high (49%), despite the fact that most of the patients (80%) were educated about the limit on duration of use. Use of intranasal glucocorticosteroids was inversely related to being an overuser (odds ratio 0.24 [95% CI, 0.17-0.35]). The risk of intranasal decongestant overuse also was reduced by use of other medications (oral H1 antihistamines and decongestants), use of nasal saline solution, and more symptoms of itchy and/or runny eyes or colored mucus. Risk was increased by a more severely blocked nose, longer duration of symptoms, the presence of sleep disturbance, higher body mass index, and previous advice to limit the duration of intranasal decongestant use. Conclusion Half of the individuals self-medicating persistent rhinitis overused intranasal decongestants, despite the fact that they were educated about the limit on duration of use.

AIM: Few well-designed randomized controlled trials (RCT) regarding the impact of community pharmacist interventions on pharmacotherapeutic monitoring of patients with Chronic Obstructive Pulmonary Disease (COPD) have been conducted. We assessed the effectiveness of a pharmaceutical care program for patients with COPD. METHODS: The PHARMACOP-trial is a single-blind 3-month RCT, conducted in 170 community pharmacies in Belgium, enrolling patients prescribed daily COPD medication, aged ≥50 years, and with a smoking history ≥10 pack-years. A computer-generated randomization sequence allocated patients to intervention (n=371), receiving protocol-defined pharmacist care, or control group (n=363), receiving usual pharmacist care (1:1 ratio, stratified by center). Interventions, focusing on inhalation technique and adherence to maintenance therapy, were carried out at start of the trial and at one month follow-up. Primary outcomes were inhalation technique and medication adherence. Secondary outcomes were exacerbation rate, dyspnea, COPD specific and generic health status and smoking behavior. RESULTS: From December 2010 to April 2011, 734 patients were enrolled. 42 patients (5.7%) were lost to follow-up. At the end of the trial, inhalation score (Mean estimated difference [Δ],13.5%; 95% Confidence Interval [CI], 10.8-16.1; P

Background: In this study, we aimed to (i) determine the prevalence of potentially inappropriate prescribing (PIP) in community-dwelling older polypharmacy patients using the Ghent Older People's Prescriptions community-Pharmacy Screening (GheOP³S) tool, (ii) identify the items that account for the highest proportion of PIP and (iii) identify the patient variables that may influence the occurrence of PIP. Additionally, pharmacist-physician contacts emerging from PIP screening with the GheOP³S tool and feasibility of the GheOP³S tool in daily practice were evaluated. Methods: A prospective observational study was carried out between December 2013 and July 2014 in 204 community pharmacies in Belgium. Patients were eligible if they were (i) ≥70 years, (ii) community-dwelling, (iii) using ≥5 chronic drugs, (iv) a regular visitor of the pharmacy and (v) understanding Dutch or French. Community pharmacists used a structured interview to obtain demographic data and medication use and subsequently screened for PIP using the GheOP³S tool. A Poisson regression was used to investigate the association between different covariates and the number of PIP. Results: In 987 (97%) of 1016 included patients, 3721 PIP items were detected (median of 3 per patient; inter quartile range: 2-5). Most frequently involved with PIP are drugs for the central nervous system such as hypnosedatives, antipsychotics and antidepressants. Risk factors for a higher PIP prevalence appeared to be a higher number of drugs (30% extra PIPs per 5 extra drugs), female gender (20% extra PIPs), higher body mass index (BMI, 20% extra PIPs per 10-unit increase in BMI) and poorer functional status (30% extra PIPs with 6-point increase). The feasibility of the GheOP³S tool was acceptable although digitalization of the tool would improve implementation. Despite detecting at least one PIP in 987 patients, only 39 physicians were contacted by the community pharmacists to discuss the items. Conclusion: A high prevalence of PIP in community-dwelling older polypharmacy patients in Belgium was detected which urges for interventions to reduce PIP.

Few analytical techniques allow to evaluate the inclusion yield of cyclodextrin-drug complexes, because most manufacturing processes give amorphous products. In this study, we have developed an alternative method to differential scanning calorimetry, to accurately determine the free/complexed piroxicam ratio by UV spectroscopy. This method is based on the differential solubility of the piroxicam-beta-cyclodextrin 1:2.5 mol/mol complex in water-acetonitrile (1:1, v/v) (Solvent A) or in anhydrous acetonitrile (Solvent B), both containing 0.05 M HCl. In anhydrous acetonitrile, beta-cyclodextrin is insoluble and the included drug remains entrapped, allowing the free piroxicam determination, while with 50% of water, the complex is totally dissolved, allowing the determination of the total guest content. This method was validated for linearity, precision and accuracy. The presence of cyclodextrin does not influence the assays, but more than 0.5% of water in Solvent B significantly affects the determination of the free piroxicam content. In comparison with differential scanning calorimetry, both detectability and precision were improved. It is now possible to analyse complexes with an inclusion purity greater than 99%.

ObjectivesThe impact of inhaled corticosteroids (ICS) on eosinophilic inflammation in asthma is well established, but their effect in a real-life setting has not been extensively studied. Our purpose was to investigate the effect of ICS on airway and systemic inflammation as well as on clinical outcomes in patients with asthma from clinical practice.Design, setting and participantsWe conducted a retrospective analysis on asthmatics from a secondary care centre in whom ICS were initiated/increased (n=101), stopped/decreased (n=60) or remained stable (n=63, used as a control group) between two visits with available sputum and blood cell counts.ResultsThe median time between both visits ranged from 1 to 2 years. Initiating or increasing ICS (median variation (IQR): 800 (400–1200) µg beclomethasone equivalent dose per day) reduced sputum eosinophils and fractional exhaled nitric oxide (P1), bronchial hyper-responsiveness and exacerbation rate was only observed in the eosinophilic phenotype (sputum eosinophils ≥3%, n=79). In non-eosinophilic asthmatics, stepping-down ICS resulted in an improvement in asthma control and quality of life, without any significant change in FEV1(n=38).ConclusionsOur results confirm the effectiveness of ICS on eosinophilic inflammation in real life and demonstrate that their clinical benefit seems to be restricted to eosinophilic asthmatics. Our data also support a try for stepping-down ICS in non-eosinophilic asthmatics.

Inclusion complexes of drugs into cyclodextrins (CDs) can be obtained at the solid state by means of supercritical dioxide (SCCO2). A successful inclusion with a yield >98.5% has been achieved with piroxicam and β-CD. The temperature and the time of exposure to SCCO2 have a significant effect on the inclusion yield while the pressure has a negative effect. However, there is a strong interaction between temperature and pressure and this interaction has a positive influence. The molar ratio piroxicam-β-CD and the addition of ternary alkaline agents were also found to be significant factors. The dissolution rate of the complexes formed using SCCO2 was found to be significantly higher than that of the physical mixture. Inclusion complexes have also been obtained with miconazole treating mixtures of miconazole, CDs and citric acid by SCCO2. This new technique of inclusion of poorly soluble drugs into CDs allows the preparation of solid complexes without using organic solvents and thus without residues.

Cyproterone acetate (CPA) is a steroidal antiandrogen with a progestogenic activity. Given that this molecule has a very poor water solubility (2.1 μg/mL), different cyclodextrins (CDs) were tested to form inclusion complexes and to increase solubility. Two different techniques were compared to study the affinity between CPA and CDs: phase-solubility studies and NMR spectroscopy. The stoichiometry and the stability constant could be determined for most complexes with the aid of phase-solubility studies. The greatest increase in solubility was achieved with the methylated β-CDs, but hydroxypropylated β- and γ-CDs also gave enhanced solubilities. 1H-NMR studies showed a solubility increase similar to that found with phase-solubility studies. The proof of inclusion in the2,6-dimethyl-β-CD (DIMEB) was shown by 1H-NMR and t-ROESY spectra.

Longitudinal trials have suggested that asthma control may be influenced by fluctuations in eosinophilic inflammation. This association has however never been confirmed in daily practice.To investigate the relationship between asthma control and sputum eosinophils in clinical practice.A retrospective longitudinal study was conducted on 187 patients with asthma with at least 2 successful sputum inductions at our Asthma Clinic. Linear mixed models were used to assess the relationship between asthma control and individual changes in sputum eosinophils. Receiver-operating characteristic curves were constructed to define minimal important differences (MIDs) of sputum eosinophils associated with a change of at least 0.5 in Asthma Control Questionnaire (ACQ) score. Then, a validation cohort of 79 patients with asthma was recruited to reassess this relationship and the accuracy of the MID values.A multivariate analysis showed that asthma control was independently associated with individual fluctuations in sputum eosinophil count (P.001). In patients with intermittent/persistently eosinophilic asthma, we calculated a minimal important decrease of 4.3% in the percentage of sputum eosinophils (area under the curve [AUC], 0.69; P.001) or 3.4-fold (AUC, 0.65; P = .003) for a significant improvement in asthma control and a minimal important increase of 3.5% (AUC, 0.67; P = .004) or 1.8-fold (AUC, 0.63; P = .02) for a significant worsening in asthma control. The association between asthma control and sputum eosinophils and the accuracy of the MIDs of sputum eosinophils were confirmed in the validation cohort.At the individual level, asthma control was associated with fluctuations in sputum eosinophil count over time.

Purpose. Piroxicam is a poorly soluble NSAID, whose solubility is enhanced when included into β-cyclodextrin. The preparation of a piroxicam-β-cyclodextrin inclusion compound using supercritical CO2 was investigated.

Few well-designed randomized controlled trials have been conducted regarding the impact of community pharmacist interventions on pharmacotherapeutic monitoring of patients with chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of a pharmaceutical care programme for patients with COPD.The pharmaceutical care for patients with COPD (PHARMACOP) trial is a single-blind 3 month randomized controlled trial, conducted in 170 community pharmacies in Belgium, enrolling patients prescribed daily COPD medication, aged ≥ 50 years and with a smoking history of ≥ 10 pack-years. A computer-generated randomization sequence allocated patients to an intervention group (n = 371), receiving protocol-defined pharmacist care, or a control group (n = 363), receiving usual pharmacist care (1:1 ratio, stratified by centre). Interventions focusing on inhalation technique and adherence to maintenance therapy were carried out at start of the trial and at 1 month follow-up. Primary outcomes were inhalation technique and medication adherence. Secondary outcomes were exacerbation rate, dyspnoea, COPD-specific and generic health status and smoking behaviour.From December 2010 to April 2011, 734 patients were enrolled. Forty-two patients (5.7%) were lost to follow-up. At the end of the trial, inhalation score [mean estimated difference (Δ),13.5%; 95% confidence interval (CI), 10.8-16.1; P0.0001] and medication adherence (Δ, 8.51%; 95% CI, 4.63-12.4; P0.0001) were significantly higher in the intervention group compared with the control group. In the intervention group, a significantly lower hospitalization rate was observed (9 vs. 35; rate ratio, 0.28; 95% CI, 0.12-0.64; P = 0.003). No other significant between-group differences were observed.Pragmatic pharmacist care programmes improve the pharmacotherapeutic regimen in patients with COPD and could reduce hospitalization rates.