Giovanni Polimeni

Data mining on electronic health record databases for signal detection in pharmacovigilance: which events to monitor?

Data mining on electronic health records (EHRs) has emerged as a promising complementary method for post‐marketing drug safety surveillance. The EU‐ADR project, funded by the European Commission, is developing techniques that allow mining of EHRs for adverse drug events across different countries in Europe. Since mining on all possible events was considered to unduly increase the number of spurious signals, we wanted to create a ranked list of high‐priority events.

Short-term memory loss associated with rosuvastatin

Memory loss and cognitive impairment have been reported in the literature in association with several 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins), but we found no published case reports associated with rosuvastatin. To our knowledge, this is the first reported case of rosuvastatin‐related short‐term memory loss. A 53‐year‐old Caucasian man with hypercholesterolemia experienced memory loss after being treated with rosuvastatin 10 mg/day. He had no other concomitant conditions or drug therapies. After discontinuation of rosuvastatin, the neuropsychiatric adverse reaction resolved gradually, suggesting a probable drug association. During the following year, the patient remained free from neuropsychiatric disturbances. Clinicians should be aware of possible adverse cognitive reactions during statin therapy, including rosuvastatin.

Allergic reactions to oral drugs : A case/non-case study from an Italian spontaneous reporting database (GIF)

Despite the wide number of studies investigating on drug-induced allergy, limited data focused on allergies associated with orally administered drugs are available. The aim of the study is to evaluate allergic drug reactions associated with oral drug use, using an Italian spontaneous reporting database of adverse drug reactions (ADRs). Spontaneous reports associated with oral drugs retrieved from seven Italian regions (GIF research group), collected from 1988 to 2006, were analysed. Association between drugs and allergic adverse reactions was assessed using the case/non-case method, calculating the ADR reporting odds ratio (ROR) as a measure of disproportionality. Overall, 27,175 reports of adverse reactions related to oral drug use were analysed; of these, 3143 (11.6%) were judged as allergy cases. Paediatric patients (<or=15 years) and inpatients (p<0.001) were more represented in cases than in non-cases. Antibiotics and Non-Steroidal Anti-inflammatory Drugs (NSAIDs) were the only two drug classes associated with a significant increase of ROR. Regarding antibiotics, cinoxacin (6.88; 95%CI 4.19-11.29) and moxifloxacin (4.20; 95% CI 3.19-5.55) were related to the highest ROR values, while propionic acid derivates (ROR 2.75; 95% CI 2.30-3.28), and in particular ibuprofen (4.20; 95% CI 3.13-5.63), have shown the highest ROR values among NSAIDs. The results of the present paper confirm the higher frequency of allergic reactions with oral antibiotics and NSAIDs, although more data are needed. Given the widespread use of these drug classes (some of them being purchased as over the counter drugs), awareness should be raised among patients and prescribers about these risks.

Nicolau Syndrome Following Etanercept Administration

Nicolau syndrome (NS), or embolia cutis medicamentosa, is a well-known but rare adverse effect of a still largely unidentified pathogenesis, observed primarily after the intramuscular administration of various drugs. NS is characterized by immediate excruciating pain, early pallor and erythema and oedema at the injection site, followed by cutaneous, subcutaneous and even muscular aseptic necrosis in a livedoid pattern. It is a potentially serious reaction that is little influenced by which drug is injected.A case is reported of NS following a subcutaneous self-injection of etanercept for psoriasis and psoriatic arthritis. This case is remarkable because NS developed after subcutaneous and not after intramuscular drug administration, and because no cases of NS following the injection of tumour necrosis factor alpha inhibitors have been reported in the literature or in the World Health Organization adverse drug reactions database. Although not directly linked to the drug, the occurrence of NS has to be considered in patients receiving biological agents.

A semantic approach for the homogeneous identification of events in eight patient databases: A contribution to the European eu-ADR project

The overall objective of the eu-ADR project is the design, development, and validation of a computerised system that exploits data from electronic health records and biomedical databases for the early detection of adverse drug reactions. Eight different databases, containing health records of more than 30 million European citizens, are involved in the project. Unique queries cannot be performed across different databases because of their heterogeneity: Medical record and Claims databases, four different terminologies for coding diagnoses, and two languages for the information described in free text. The aim of our study was to provide database owners with a common basis for the construction of their queries. Using the UMLS, we provided a list of medical concepts, with their corresponding terms and codes in the four terminologies, which should be considered to retrieve the relevant information for the events of interest from the databases.

Gynecomastia possibly induced by rosuvastatin.

Gynecomastia is characterized by benign progressive enlargement of the male breast. A pharmacologic origin is identified in 10–20% of cases. Several case reports have associated this condition to the use of statins. However, to our knowledge, no case of rosuvastatin‐induced gynecomastia has been reported in the literature. We describe a 57‐year‐old man who developed bilateral gynecomastia after 2 months of rosuvastatin therapy. After switching to a different statin, atorvastatin, his symptoms resolved within 1 month. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship between the patients development of gynecomastia and rosuvastatin therapy. The relatively strong effect of rosuvastatin on inhibiting steroidogenesis might have explained why our patients gynecomastia occurred only with this agent. Clinicians should be aware of the possibility of adverse endocrine reactions when statins are prescribed, including newer agents such as rosuvastatin.

Design and evaluation of a semantic approach for the homogeneous identification of events in eight patient databases: a contribution to the European EU-ADR project

The overall objective of the EU-ADR project is the design, development, and validation of a computerised system that exploits data from electronic health records and biomedical databases for the early detection of adverse drug reactions. Eight different databases, containing health records of more than 30 million European citizens, are involved in the project. Unique queries cannot be performed across different databases because of their heterogeneity: Medical record and Claims databases, four different terminologies for coding diagnoses, and two languages for the information described in free text. The aim of our study was to provide database owners with a common basis for the construction of their queries. Using the UMLS, we provided a list of medical concepts, with their corresponding terms and codes in the four terminologies, which should be considered to retrieve the relevant information for the events of interest from the databases.

Neurogenic Ejaculatory Disorders: Focus on Current and Future Treatments

Ejaculation is a complex and still poorly understood neurological mechanism, at both spinal and cerebral levels as it is closely associated with orgasm. Physiologically, ejaculation is defined as the expulsion of seminal fluid from the urethral meatus and consists of two phases, namely emission and expulsion. Ejaculation is mediated by a spinal control center, referred to as a spinal pattern generator that coordinates sympathetic, parasympathetic and motor (somatic) outflows, integrating the latter with the inputs from the supraspinal sites in brainstem, hypothalamus and preoptic area. Premature ejaculation (PE) is the most common sexual dysfunction among young men, and it has been considered mostly psychogenic in origin, although it can be associated to diverse urological and neurological diseases. On the contrary, retrograde ejaculation and anejaculation are predominantly related to organic causes, particularly to neurogenic ones. Since ejaculation is mostly a spinal reflex, it is comprehensible that ejaculatory disorders are more frequent in spinal cord injury than in other neurological disorders. Over the past decades, research has focused on PE, and evidence from clinical studies showed a beneficial effect of antidepressants for the treatment of men with PE. Other ejaculatory disorders, especially painful ejaculation, have been less investigated and the proper therapy is still controversial. Aim of this review is to provide a comprehensive description of both currently available treatments and most promising future therapies, including assigned patents, for the neurogenic ejaculatory disorders.

Adverse reactions induced by NSAIDs and antibacterials: analysis of spontaneous reports from the Sicilian regional database.

AbstractObjectives: To (i) evaluate the suspected adverse drug reactions (ADRs) related to NSAIDs and antibacterials that were reported to Sicilian local health officers by healthcare professionals; and (ii) to detect new or serious potential signals of alarm related to these two widely used drug categories. Methods: We selected all the spontaneous reports of ADRs sent between January 1998 and June 2004 and analysed those attributed to NSAIDs and systemic antibacterials, applying proportional reporting ratio (PRR) methodology. PRRs >2, χ2 >4 and >3 ADRs were regarded as signals. Results: During the period considered, 1585 reports of ADRs were received overall (42.6% serious), with an annual reporting rate of approximately 49.1 reports per million inhabitants on average; 351 referred to systemic antibacterials, and 179 to NSAIDs. There were 174 (49.6%) reports of serious ADRs associated with antimicrobials and 108 (60.3%) associated with NSAIDs. Disproportionality was observed, in particular for anaphylactic shock induced by ceftriaxone (all reports were associated with off-label use of the drug), photosensitivity reaction induced by lomefloxacin (administered in the summer), hepatitis induced by nimesulide (three cases leading to liver transplantation) and vasculitis induced by nimesulide. Conclusion: Our analysis highlighted several signals of alarm deserving further investigation or measures to influence prescribing. This study underlines the value of a regional centre in identifying local factors (such as prescribing patterns) that may increase the prevalence of serious ADRs.

Embolia cutis medicamentosa following thiocolchicoside injection.

© 2008 The Authors 1005 JEADV 2008, 22 , 1003–1030 Journal compilation