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cited By 1; International audience; Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures). © 2018 Société Nationale Française de Médecine Interne (SNFMI)

PURPOSE: This study aims to explore the differences in reported information between adverse drug reaction (ADR) reports of patient and healthcare professionals (HCPs), and, in addition, to explore possible correlation between the reported elements of information.METHODS: This retrospective study compared the reported information between 200 ADR reports of patients and HCPs. Reports were rendered anonymous and scored for the presence or absence of predefined elements of information. These elements can be objective (e.g. start date of the ADR) or subjective (e.g. the impact or severity of the ADR). A two-sided Pearson's Chi-square test was used to detect statistically significant differences in the reported information. A Bonferroni correction was used to correct for multiple comparisons. Correlation between the elements of information was explored using categorical principal components analysis (CATPCA).RESULTS: Overall, HCPs had a higher score for the presence of objective and patients for subjective elements of information. Elements that were statistically significant more often reported by patients are the impact of the ADR and the patient's weight and height. HCPs statistically significant more often reported the medical history and the route of administration of the drug. CATPCA showed four clusters of elements of information that have fair correlation.CONCLUSIONS: This study demonstrates the differences in reported information between ADR reports of patients and HCPs. Patient reports are more focused on patient-related information and the impact of the reported ADRs, whereas reports from HCPs provide more clinically related information. Copyright © 2014 John Wiley & Sons, Ltd.

Objective: Change Pain Latin America (CPLA) was created to enhance chronic pain understanding and develop pain management improving strategies in this region. During its seventh meeting (August 2016), the main objective was to discuss tramadol’s role in treating pain in Latin America. Furthermore, potential pain management consequences were considered, if tramadol was to become more stringently controlled. Methods: Key topics discussed were: main indications for prescribing tramadol, its pharmacological characteristics, safety and tolerability, effects of restrictions on its availability and use, and consequent impact on pain care quality. Results: The experts agreed that tramadol is used to treat a wide spectrum of non-oncological pain conditions (e.g. post-surgical, musculoskeletal, post-traumatic, neuropathic, fibromyalgia), as well as cancer pain. Its relevance when treating special patient groups (e.g. the elderly) is recognized. The main reasons for tramadol’s high significance as a treatment option are: its broad efficacy, an inconspicuous safety profile and its availability, considering that access to strong analgesics–mainly controlled drugs (classical opioids)–is highly restricted in some countries. The CPLA also agreed that tramadol is well tolerated, without the safety issues associated with long-term nonsteroidal anti-inflammatory drug (NSAID) use, with fewer opioid-like side effects than classical opioids and lower abuse risk. Conclusions: In Latin America, tramadol is a valuable and frequently used medication for treating moderate to severe pain. More stringent regulations would have significant impact on its availability, especially for outpatients. This could cause regression to older and frequently inadequate pain management methods, resulting in unnecessary suffering for many Latin American patients. © 2017 Informa UK Limited, trading as Taylor and Francis Group.

cited By 2; International audience; What is known and objective: The complex dose regimens of the direct-acting oral anticoagulants (DOAC) make their appropriate prescribing highly challenging. Inappropriate prescribing of the DOAC remains poorly addressed. We studied the patterns of DOAC prescription and estimated the prevalence of drug-related problems (DRPs) associated with their use. Methods: A cross-sectional study was conducted using data from medical records system of the Lyon teaching hospitals. DRPs, identified among patients who received a DOAC, between 1 January 2010 and 31 July 2013, were categorized according to the Pharmaceutical Care Network Europe Classification System. The prevalence of hospital stays with a DRP was estimated, and a subgroup analysis according to DOAC and their indication for use was provided. Clinical outcomes were not assessed. Results: Of the 4154 hospital stays with at least one DOAC administration [3412 patients; median age (range): 71 years (14–98), 57% female], 70·8% were excluded from the analysis mainly due to missing information for renal function and/or patient weight. Of the 1188 hospital stays that were screened, 100 DRPs were identified (prevalence 8·4%; 95% CI, 6·8–10·0). The highest prevalence was found among patients who received rivaroxaban for atrial fibrillation (14·6%; 95% CI, 10·7–18·5). A too low drug dose was the most frequent DRP (n = 56; 4·7%), followed by a too high drug dose (n = 37; 3·1%), contraindication (n = 5; 0·4%), and pharmacokinetic problem requiring dose adjustment (n = 2; 0·2%). What is new and conclusion: Drug-related problems associated with the DOACs occur quite commonly among hospitalized patients. Although these DRPs were considered to be of minor severity, prescribing protocols to support better prescribing should be disseminated to reduce the risk to patients. Renal function and body weight data should be mandatory on prescriptions to allow cross-checking. © 2016 John Wiley & Sons Ltd

Background: A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy guidance. Methods: Patients with a CGI-S = 4 and requiring antidepressant medication de novo or changes in their medication regime were recruited at 18 Spanish public hospitals, genotyped with a commercial PGx panel (Neuropharmagen®), and randomized to PGx-guided treatment (n = 155) or treatment as usual (TAU, control group, n = 161), using a computer-generated random list that locked or unlocked psychiatrist access to the results of the PGx panel depending on group allocation. The primary endpoint was the proportion of patients achieving a sustained response (Patient Global Impression of Improvement, PGI-I = 2) within the 12-week follow-up. Patients and interviewers collecting the PGI-I ratings were blinded to group allocation. Between-group differences were evaluated using ?2-test or t-test, as per data type. Results: Two hundred eighty patients were available for analysis at the end of the 12-week follow-up (PGx n = 136, TAU n = 144). A difference in sustained response within the study period (primary outcome) was not observed (38.5% vs 34.4%, p = 0.4735; OR = 1.19 [95%CI 0.74-1.92]), but the PGx-guided treatment group had a higher responder rate compared to TAU at 12 weeks (47.8% vs 36.1%, p = 0.0476; OR = 1.62 [95%CI 1.00-2.61]), and this difference increased after removing subjects in the PGx-guided group when clinicians explicitly reported not to follow the test recommendations (51.3% vs 36.1%, p = 0.0135; OR = 1.86 [95%CI 1.13-3.05]). Effects were more consistent in patients with 1-3 failed drug trials. In subjects reporting side effects burden at baseline, odds of achieving a better tolerability (Frequency, Intensity and Burden of Side Effects Rating Burden subscore =2) were higher in the PGx-guided group than in controls at 6 weeks and maintained at 12 weeks (68.5% vs 51.4%, p = 0.0260; OR = 2.06 [95%CI 1.09-3.89]). Conclusions: PGx-guided treatment resulted in significant improvement of MDD patient's response at 12 weeks, dependent on the number of previously failed medication trials, but not on sustained response during the study period. Burden of side effects was also significantly reduced. © 2017 The Author(s).

Objectives: To identify differences in the recommendations for targeted cancer therapies (TCT) in three distinctive European health care systems: Serbian, Scottish and Dutch, and to examine the role of cost effectiveness analyses (CEA) in such recommendations. Methods: A list of currently approved TCTs cited from the European Medicines Agency (EMA) was cross-referenced with the drug reimbursement reports issued by Health Insurance Fund (RFZO) for Serbia, Scottish Medicines Consortium (SMC) for Scotland and Health Institute (ZI) for the Netherlands. The following key variables were gathered from the reports: drug indication, registration status, reimbursement status and outcome of the cost effectiveness evaluation. Results: There were 44 TCTs indicated for 75 cancer sites and approved by EMA. Out of total number of drugs per indication (d/i= 75), 20 were reimbursed in Serbia, and 15 are still without the decision from RFZO. Remaining majority of TCTs is not registered in Serbia. None of submissions neither CEAs were publically available. SMC positively assessed 25 d/i and rejected as much as 30. All appraisals were published, and majority contained full CEAs. Finally, Dutch ZI accepted total of 59 d/i and disapproved use of only 5 d/i. The majority of reimbursed drugs were exempted from CEA in accordance with the policy for expensive hospital drugs. Conclusions: Although data collected for Serbia did not allow us to evaluate practiced policy in broader extent, it is certainly surrounding with the smallest number of reimbursed TCTs. Surprisingly, TCTs in Scotland were comparable to this number, yet reasons for such an outcome were fairly different. It seems that full application of CEA in TCTs submission contributed to 55% of SMC negative recommendations. Its Dutch counterpart, ZI, issued only 8% of negative decisions to TCTs. The mode for a success rate in the Netherlands was special policy that enabled reimbursement of TCTs without CEA.

Latin America contributes 1–1.2 million clinical malaria cases to the global malaria burden of about 300 million per year. In 21 malaria endemic countries, the population at risk in this region represents less than 10% of the total population exposed worldwide. Factors such as rapid deforestation, inadequate agricultural practices, climate change, political instability, and both increasing parasite drug resistance and vector resistance to insecticides contribute to malaria transmission. Recently, several malaria endemic countries have experienced a significant reduction in numbers of malaria cases. This is most likely due to actions taken by National Malaria Control Programs (NMCP) with the support from international funding agencies. We describe here the research strategies and activities to be undertaken by the Centro Latino Americano de Investigacion en Malaria (CLAIM), a new research center established for the non-Amazonian region of Latin America by the National Institute of Allergy and Infectious Diseases (NIAID). Throughout a network of countries in the region, initially including Colombia, Guatemala, Panama, and Peru, CLAIM will address major gaps in our understanding of changing malaria epidemiology, vector biology and control, and clinical malaria mainly due to Plasmodium vivax . In close partnership with NMCPs, CLAIM seeks to conduct research on how and why malaria is decreasing in many countries of the region as a basis for developing and implementing new strategies that will accelerate malaria elimination.

In their Original Investigation published in a recent issue of JAMAInternal Medicine, Prasad and Mailankody examine the costs of bringing a single drug with an oncological indication to the market. They conclude that 10 selected companies had a median investment cost of $648 million for the development of their drug, whereas the median revenue in 4 years on average was $1658.4 million. This further reinforces the notion that there are large profits to be made with drug development, and that current pharmaceutical drug prices are unrelated to the actual costs for research and development.

Pain is frequent in diabetic neuropathy and is very hard to manage. Antiepileptic drugs have been used in treating pain for several decades. Their effectiveness has been described in different types of neuropathic pain, but when used as analgesics in painful diabetic neuropathy it still remains controversial. To clarify this effectiveness, a meta-analysis was performed to determine which antiepileptic drug had the best analgesic potential for managing pain in patients suffering from painful diabetic neuropathy. The search covered the Cochrane, MEDLINE, EMBASE, and LILACS databases, between January 1966 and September 2005. The following information was obtained from each article: criteria for diagnosing diabetic neuropathy, patients' age average, antiepileptic drug received and dose, sample size, duration of the disease and treatment follow-up, outcome measurement, evaluation of pain, and rescue medication. A combined 2.33 relative risk (95% confidence interval [CI] 1.88-2.88) was obtained; this result indicated that the antiepileptic drugs studied were effective for controlling pain in diabetic neuropathy. The corresponding necessary number to treat (NNT) values were established for evaluating which antiepileptic drug was most effective as an analgesic, according to our interests; pregabalin was shown to be the antiepileptic drug having the lowest NNT (NNT = 3.24 and 95% CI 2.12-6.81) for achieving greater than 50% analgesia in patients suffering from painful diabetic neuropathy. Antiepileptic drugs are frequently used in the specific case of diabetic neuropathy; the combined result of this meta-analysis has demonstrated their analgesic benefit. © 2007 U.S. Cancer Pain Relief Committee.

Background: Adverse Drug reactions (ADR) cause a high number of deaths among hospitalized patients in developed countries. Major drug agencies have devoted a great interest in the early detection of ADRs due to their high incidence and increasing health care costs. Reporting systems are available in order for both healthcare professionals and patients to alert about possible ADRs. However, several studies have shown that these adverse events are underestimated. Our hypothesis is that health social networks could be a significant information source for the early detection of ADRs as well as of new drug indications. Methods: In this work we present a system for detecting drug effects (which include both adverse drug reactions as well as drug indications) from user posts extracted from a Spanish health forum. Texts were processed using MeaningCloud, a multilingual text analysis engine, to identify drugs and effects. In addition, we developed the first Spanish database storing drugs as well as their effects automatically built from drug package inserts gathered from online websites. We then applied a distant-supervision method using the database on a collection of 84,000 messages in order to extract the relations between drugs and their effects. To classify the relation instances, we used a kernel method based only on shallow linguistic information of the sentences. Results: Regarding Relation Extraction of drugs and their effects, the distant supervision approach achieved a recall of 0.59 and a precision of 0.48. Conclusions: The task of extracting relations between drugs and their effects from social media is a complex challenge due to the characteristics of social media texts. These texts, typically posts or tweets, usually contain many grammatical errors and spelling mistakes. Moreover, patients use lay terminology to refer to diseases, symptoms and indications that is not usually included in lexical resources in languages other than English. This work was supported by TrendMiner project [FP7-ICT287863] and by MULTIMEDICA project [TIN2010-20644-C03-01].

PURPOSE: This study aims to explore the differences in reported information between adverse drug reaction (ADR) reports of patient and healthcare professionals (HCPs), and, in addition, to explore possible correlation between the reported elements of information. METHODS: This retrospective study compared the reported information between 200 ADR reports of patients and HCPs. Reports were rendered anonymous and scored for the presence or absence of predefined elements of information. These elements can be objective (e.g. start date of the ADR) or subjective (e.g. the impact or severity of the ADR). A two-sided Pearson's Chi-square test was used to detect statistically significant differences in the reported information. A Bonferroni correction was used to correct for multiple comparisons. Correlation between the elements of information was explored using categorical principal components analysis (CATPCA). RESULTS: Overall, HCPs had a higher score for the presence of objective and patients for subjective elements of information. Elements that were statistically significant more often reported by patients are the impact of the ADR and the patient's weight and height. HCPs statistically significant more often reported the medical history and the route of administration of the drug. CATPCA showed four clusters of elements of information that have fair correlation. CONCLUSIONS: This study demonstrates the differences in reported information between ADR reports of patients and HCPs. Patient reports are more focused on patient-related information and the impact of the reported ADRs, whereas reports from HCPs provide more clinically related information. Copyright © 2014 John Wiley & Sons, Ltd.

This paper presents a cost analysis of the utilisation of infliximab for the treatment of Crohn's disease. The indication for infliximab for Dutch Crohn patients is an active disease with insufficient improvement on adequate therapy with corticosteroids and/or immunosuppressive therapy. We compared direct health-care costs (hospital and community pharmacy) before and after first infliximab treatment for 21 Crohn patients in the University Hospital Groningen who started infliximab during 1 January 2000 to 15 march 2001. Our study design was observational and patients served as their own controls with similar periods before and after infliximab per patient considered (minimally 3 months before and 3 months after infliximab). Drug costs for infliximab (including administration) were estimated at € 5800,- per patient-year. Excluding infliximab costs, costs per patient-year were € 6400,- and € 8600,-before and after first infliximab treatment, respectively. In both periods, the majority of the other costs was related to hospitalization. Also, drug costs in the community pharmacy were estimated to contribute relevant shares. Other researchers have found decreases in medical costs after the start of infliximab treatment. We found the opposite development. More experience and routine with infliximab treatment may lower costs in the future.

Drug therapy in cystic fibrosis is focused on pulmonary infection and inflammation, intestinal obstruction and the substitution of pancreas enzymes. Most morbidity and mortality arises from the pulmonary infection and subsequent tissue destruction and deterioration of lung function. Antibiotic treatment is the mainstay of therapy. Nebulised antibiotics improve lung function and the incidence of acute exacerbations is reduced in patients chronically infected with Pseudomonas. Macrolides play a special role probably due to an antiinflammatory effect. Inhalation of rhDNAse improves lung function and decreases deterioration of lung function. New therapeutics directed at the CFTR defect are not yet available. Pharmacokinetics in CF patients may differ from those in healthy volunteers, probably due to differences in body composition.

PURPOSE: Targeted cancer therapies (TCTs) are drugs that specifically act on molecular targets within the cancer cell, causing its regression and/or destruction. Although TCTs offer clinically important gains in survival in one of the most challenging therapeutic areas, these gains are followed by considerable increases in health care expenditures. The aim of this study was to identify differences in the recommendations for TCTs in 3 European health care systems (Serbian, Scottish, and Dutch) and to examine the role of pharmacoeconomic (PE) assessments in such recommendations.METHODS: A list of currently approved TCTs cited from the European Medicines Agency was cross-referenced with drug reimbursement reports issued by the National Health Insurance Fund for Serbia, the Scottish Medicines Consortium for Scotland, and the National Health Institute for the Netherlands. The following key variables were gathered from the reports: drug indication, registration status, reimbursement status, and outcome of the PE evaluation.FINDINGS: There were 41 TCTs approved by the European Medicines Agency for 70 cancer indications. Of the total number of TCT indications, 20 were reimbursed in Serbia, and 25 are still without a decision from the national agency. The remaining TCT indications (n = 25) are not registered in Serbia. None of the submissions or the PE analyses were publicly available. The Scottish Medicines Consortium positively assessed 26 TCT indications and rejected 30. All appraisals were published, and the majority contained full PE assessments. Finally, the Dutch agency accepted 60 TCT indications and disapproved the use of 1. The majority of reimbursed drugs were exempted from PE evaluation in accordance with 2 recent policies regarding expensive hospital drugs.IMPLICATIONS: In the 3 examined health care systems, the reimbursement status of the TCTs differed significantly. Level of PE application within the TCT evaluation procedures seemed to largely affect the final reimbursement decisions. Although, there are special policies in the Netherlands that enabled fast access for 98% of the TCTs that applied for reimbursement, a clear definition of cost-effectiveness threshold and strict requirements for full cost utility assessments in Scotland led to acceptance of only 46% of the TCT submissions. More precise PE guidelines must still be designed for TCT reimbursement in Serbia. Guidelines must account for specific epidemic and economic conditions of the country and could build on the experiences of Scotland and the Netherlands.

Respiratory drugs are widely used in children to treat labeled and non-labeled indications but only some data are available quantifying comprehensively off-label usage. Thus, we aim to analyse drug utilisation and off-label prescribing of respiratory drugs focusing on age- and indication-related off-label use. Patients aged ≤18 years documented in the Bavarian Association of Statutory Health Insurance Physicians database (approx. 2 million children) between 2004 and 2008 were included in our study. Annual period prevalence rates (PPRs) per 10,000 children and the proportion of age- and indication-related off-label prescriptions were calculated and stratified by age and gender. Within the study period, highest PPRs were found for the fixed combination of clenbuterol/ambroxol (between 374-575 per 10,000 children) and the inhaled short acting beta-2-agonist salbutamol (between 378-527 per 10,000 children). Highest relative PPR increase was found for oral salbutamol (approx. 39-fold) whereas the most distinct decrease was found for oral long-acting beta-2-agonist clenbuterol (-97%). Compound classes most frequently involved in off-label prescribing were inhaled bronchodilative compounds (91,402; 37.3%) and oral beta-2-agonists (26,850; 22.5%). The highest absolute number of off-label prescriptions were found for inhaled salbutamol (n = 67,084; 42.0%) and oral clenbuterol/ambroxol (fixed combination, n = 18,897; 20.7%). Off-label prescribing due to indication was of much greater relevance than age-related off-label use. Most frequently, bronchodilative compounds were used off-label to treat respiratory tract infections. Highest off-label prescription rates were found in the youngest patients without relevant gender-related differences. Off-label prescribing of respiratory drugs is common especially in young children. Bronchodilative drugs were most frequently used off-label for treating acute bronchitis or upper respiratory tract infections underlining the essential need for a more rational prescribing in this area. © 2014 Schmiedl et al.

Graphical abstractDisplay Omitted HighlightsDrugs and adverse reactions (ADRs) were clustered by a biclustering approach.ADR mechanisms were inferred for the clusters with drug indications.Some ADR cases were attributed to the patient's physiological backgrounds. A big challenge in pharmacology is the understanding of the underlying mechanisms that cause drug-induced adverse reactions (ADRs), which are in some cases similar to each other regardless of different drug indications, and are in other cases different regardless of same drug indications. The FDA Adverse Event Reporting System (FAERS) provides a valuable resource for pharmacoepidemiology, the study of the uses and the effects of drugs in large human population. However, FAERS is a spontaneous reporting system that inevitably contains noise that deviates the application of conventional clustering approaches. By performing a biclustering analysis on the FAERS data we identified 163 biclusters of drug-induced adverse reactions, counting for 691ADRs and 240 drugs in total, where the number of ADR occurrences are consistently high across the associated drugs. Medically similar ADRs are derived from several distinct indications for use in the majority (145/163=88%) of the biclusters, which enabled us to interpret the underlying mechanisms that lead to similar ADRs. Furthermore, we compared the biclusters that contain same drugs but different ADRs, finding the cases where the populations of the patients were different in terms of age, sex, and body weight. We applied a biclustering approach to catalogue the relationship between drugs and adverse reactions from a large FAERS data set, and demonstrated a systematic way to uncover the cases different drug administrations resulted in similar adverse reactions, and the same drug can cause different reactions dependent on the patients' conditions.

BACKGROUND: In chronic inpatients polypharmacy is common and sometimes the combinations of psychotropics are irrational from a theoretical point of view. AIMS Registration of polypharmacy and irrational combinations in clinical practice. METHODS: In this descriptive study of 127 longstay patients in a psychiatric hospital we registrated the frequency of polypharmacy, the number of irrational combinations of psycho tropics and the reasons to describe these combinations. We tried to find a relation with the type of housing (an indirect measure for the intensity of care) and to the DSM-IV diagnosis. RESULTS: We found the use of four or five psychotropics in 24% of the population, in these cases we found irrational combinations in 89%. This group mainly consisted of patients with (partial) therapy-resistant schizophrenia of the undifferentiated and disorganised subtype and with schizo-affective disorder. In the total group of users of four and five psychotropics we found relatively more premorbid personality disorders and mild mental retardation. The percentage of users of four and five psychotropics increased with the intensity of care. Irrational combinations were mainly the result of long-lasting treatment of complex symptomatology. Following literature, a list of possible treatments in case of therapy resistance and conduct disorders is given. The authors give recommendations for further research on addition with a second high-potency antipsychotic drug in the case of therapy resistance for clozapine, and for fostering the quality of prescribing low-potency antipsychotic drugs and benzodiazepines for addition in the case of conduct disorders. CONCLUSIONS: Polypharmacy and irrational combinations occur frequently in chronic inpatients and seem inevitable.