Frank Rouby

Assessment of abuse potential of benzodiazepines from a prescription database using ‘doctor shopping’ as an indicator

AbstractBackground: Benzodiazepines are widely used for different purposes because of their pharmacological properties, but their abuse potential may represent a limitation to their use. Data suggest that this abuse potential may vary between products and available dosages. Doctor shopping (the simultaneous use of several physicians by a patient) is one of the most important ways in which prescription drugs, in particular benzodiazepines, are diverted. Objective: To assess the potential for abuse of several benzodiazepines using doctor shopping in a French administrative area as a proxy for abuse. Methods: All prescriptions reimbursed during the year 2003 in Haute-Garonne, France (one million inhabitants) for benzodiazepines that were available in ambulatory care through community pharmacies as solid oral forms were extracted from a reimbursement database. The benzodiazepines were alprazolam (0.25 mg, 0.50 mg), bromazepam 6 mg, clonazepam 2mg, clorazepate (5mg, 10 mg, 50 mg), diazepam (1 mg, 5 mg, 10 mg), flunitrazepam 1 mg, lorazepam (1 mg, 2.5 mg) and tetrazepam 50 mg. For each patient, the quantities prescribed, dispensed and obtained by doctor shopping (i.e. overlap between prescriptions from different prescribers) were computed. Benzodiazepines were compared using their ‘doctor shopping indicator’ (DSI, the percentage of each drug obtained through doctor shopping among the total reimbursed quantity). Results: About 128 000 patients received at least one benzodiazepine during the year. Four groups of benzodiazepines were identified according to their abuse potential: very high abuse potential (flunitrazepam, DSI = 42.8%); high abuse potential (diazepam 10 mg, DSI = 3.2%; clorazepate 50 mg, DSI = 2.7%); intermediate abuse potential (alprazolam 0.50 mg, bromazepam, clonazepam, DSI ranging from 1.8% to 1.9%); and low abuse potential (other benzodiazepines and dosages, DSI ranging from 0.3% to 1.1%). Conclusion: The DSI can be used to assess the relative abuse liability of benzodiazepines and to detect signals of new patterns of abuse in settings where centralized records of prescription or deliveries are available for the great majority of patients.

Amygdala activity correlates with attentional bias in PTSD.

Post-traumatic stress disorder (PTSD) is an anxiety disorder arising in the aftermath of a traumatic event. The most prevalent hypothesis is that of an increased amygdala activity to threat cues. The amygdala has also shown an implication in orienting attention toward threat. The aim of the study was to explore the correlations between amygdala activity, symptom severity and attentional bias in PTSD. Patients and healthy controls were assayed on an fMRI emotional face matching task and an attentional detection of target (DOT) task. The amygdala showed enhanced activity in PTSD (vs. controls). It positively correlated with anxiety scores and PTSD symptomatology. It also positively correlated with the disengagement index. Mostly, these results provide preliminary support for an implication of the amygdala in attention orientation to threat in PTSD. These results are further discussed in light of recent theories concerned with cortico-limbic functioning.

Estimation of clonazepam abuse liability: a new method using a reimbursed drug database.

Some observations suggest the existence of clonazepam abuse. The aim of this study was to assess its magnitude in real life by a new method, using a prescription database, and to assess its evolution between 2001 and 2006. Individuals from a region affiliated to the French health reimbursement system, who had a prescription of clonazepam reimbursed between 1 January and 15 February of two selected years were included. Their deliveries were monitored over a 9-month period. After a descriptive analysis, a clustering method illustrated by a factorial analysis was used to identify different subgroups of clonazepam consumers. An increase of 82% in participants who had a delivery of clonazepam between 2001 and 2006 was observed. Using the clustering method, this study identified some deviant participants. This group comprises a higher proportion of males, benzodiazepine users, and buprenorphine users. The number of deliveries by different prescribers and pharmacies are higher. The proportion of deviant participants increased between 2001 and 2006 (from 0.86 to 1.38%). Our method can be used to assess the magnitude of abuse liability of clonazepam and is also interesting for following its evolution, two important keys for assessing patterns of abuse.

Use of intravenous immunoglobulins in clinical practice: data from three French university hospitals

Since several years, the use of intravenous immunoglobulins (IVIg) has increased. This growth has encouraged some countries to publish guidelines. In parallel, some countries have conducted audits to know how IVIg are used in clinical practice in the light of the available guidelines. The objective of this study was to assess IVIg use in three French university hospitals in 2006. All IVIg administrations were evaluated during 6 months (12 September 2005–12 March 2006) in French university hospitals of Marseille. Different data were recorded for each administration: patient characteristics, indication, formulation and quantity. During the study period, 2802 administrations of IVIg (corresponding to a total quantity of 76 780 g) have been recorded. Four hundred and thirty‐five patients received at least one of these administrations. The five most reported indications were multifocal motor neuropathy (11.0% of total quantity), chronic inflammatory demyelinating polyradiculoneuropathy (10.2%), corticoresistant dermatomyositis (10.2%), immune thrombocytopaenia (9.9%) and primary immune deficiency (9.1%). According to available French recommendations, 70% of the IVIg use was for ‘acknowledged indications’, 9% for ‘indications to be assessed’ and 18% for ‘unwarranted indications’. The 10 most reported indications were ‘acknowledged indications’ according to available recommendations of the French expert group. Nevertheless, the two most reported indications were not approved by the French Health Products Agency (AFSSAPS) at the time of the study and were approved since.

Pyoderma gangrenosum arising during treatment of psoriasis with adalimumab: Effectiveness of ustekinumab

1. Lowitt M, Dover J. Necrobiosis lipoidica. J. Am. Acad. Dermatol. 1991; 25: 735–48. 2. Reid S, Ladizinski B, Lee K et al. Update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment options. J. Am. Acad. Dermatol. 2013; 69: 783–91. 3. Sibbald C, Reid S, Alavi A. Necrobiosis lipoidica. Dermatol. Clin. 2015; 33: 343–60. 4. Gebauer K, Armstrong M. Kobner phenomenon with necrobiosis lipoidica diabeticorum. Int. J. Dermatol. 1993; 32: 895–6. 5. Khunger N, Molpariya A, Khunger A. Complications of tattoos and tattoo removal: stop and think before you ink. J. Cutan. Aesthet. Surg. 2015; 8: 30–6. 6. Wood A, Hamilton S, Wallace W et al. Necrobiotic granulomatous tattoo reaction. Am. J. Dermatopathol. 2014; 36: e152–5. 7. Babin-muise D, Miller R, Murray S et al. Necrobiosis lipoidica diabeticorum in a tattoo site. J. Cutan. Med. Surg. 2012; 16: 286–7.

Comment on “Patient Reporting in the EU: Analysis of EudraVigilance Data”

We read with interest the work by Banovac et al. [1] describing the evolution of patient reporting before and after the latest European pharmacovigilance regulation became operational in 2012. For the first time in the European Union (EU), and over a 6-year period, they compare patient and healthcare professional (HCP) reports according to different types of data such as adverse drug reaction (ADR) type, reported substances, indication, and demographic characteristics of patients. They confirm that patient reports complement those performed by HCPs in terms of reported System Organ Class (SOC) and reported substances. They also give a real overview of patient reporting in the EU, which is very welcomed. Patient reporting of ADRs has become one of the challenges of 21st century pharmacovigilance [2]. Indeed, patients are increasingly involved in pharmacovigilance reporting systems worldwide and patient voice is given more and more consideration by health authorities and marketing authorization holders (MAHs). Additionally, growing initiatives from consumer organizations are being recognized as potential valuable sources of information [3]. Given an increase in patient reporting in the EU, the results of this study raise a major issue, which is the role of patient reporting and the quality of reported information. The authors acknowledge that measuring the completeness of reports (level of population of all relevant fields in an individual case safety report [ICSR]) was not in the scope of their study. As mentioned, it is a subject for future research and its impact on signal detection should be further investigated. The value of the reports as a signal is directly dependent on the amount of clinically relevant information they include in addition to the fact that an ADR report requires a thorough examination of the potential drug–ADR association. Some studies revealed no major qualitative difference between patient and HCP reports but did not study the intrinsic quality of the reports [4]. Indeed, published data concerning patient reports and the availability of important elements of information such as time to onset of the ADR, concomitant medication, medical history, or outcome are scarce [5–7]. In a 5-year study conducted on patient reports received after French legislation legally authorized patient reporting in June 2011, we recently reported that several elements of information needed for a proper assessment of ADR are not always provided in patient reports. Completeness of 16 key elements of information (including drug start and end date, duration of treatment, time to onset and duration of the ADR, outcome, medical history, and concomitant medication) was assessed in initial patient reports. The mean number of available key elements of information in initial reports was 11 of 16. Time to onset and duration of the ADR were respectively available in only 51 and 58% of the reports. Medical history and concomitant medication were This comment refers to the article available at doi:10.1007/s40264017-0534-1.

Pulmonary embolism induced by methotrexate in a dermatomyositis patient

Joint Bone Spine - In Press.Proof corrected by the author Available online since mardi 20 septembre 2016