Metadata for Data dIscoverability aNd Study rEplicability in obseRVAtional Studies (MINERVA): Development and Pilot of a Metadata List and Catalogue in Europe.

PURPOSE: Metadata for data dIscoverability aNd study rEplicability in obseRVAtional studies (MINERVA), a European Medicines Agency-funded project (EUPAS39322), defined a set of metadata to describe real-world data sources (RWDSs) and piloted metadata collection in a prototype catalogue to assist investigators from data source discoverability through study conduct. METHODS: A list of metadata was created from a review of existing metadata catalogues and recommendations, structured interviews, a stakeholder survey, and a technical workshop. The prototype was designed to comply with the FAIR principles (findable, accessible, interoperable, reusable), using MOLGENIS software. Metadata collection was piloted by 15 data access partners (DAPs) from across Europe. RESULTS: A total of 442 metadata variables were defined in six domains: institutions (organizations connected to a data source); data banks (data collections sustained by an organization); data sources (collections of linkable data banks covering a common underlying population); studies; networks (of institutions); and common data models (CDMs). A total of 26 institutions were recorded in the prototype. Each DAP populated the metadata of one data source and its selected data banks. The number of data banks varied by data source; the most common data banks were hospital administrative records and pharmacy dispensation records (10 data sources each). Quantitative metadata were successfully extracted from three data sources conforming to different CDMs and entered into the prototype. CONCLUSIONS: A metadata list was finalized, a prototype was successfully populated, and a good practice guide was developed. Setting up and maintaining a metadata catalogue on RWDSs will require substantial effort to support discoverability of data sources and reproducibility of studies in Europe.

A European multicentre drug utilisation study of the impact of regulatory measures on prescribing of codeine for pain in children.

PURPOSE: In June 2013, following recommendations from the World Health Organization (WHO) and Food and Drug Administration (FDA), the European Medicines Agency agreed updates to the codeine product information regarding use for pain in children younger than 12 years and children undergoing tonsillectomy or adenoidectomy (TA) for obstructive sleep apnoea. This study was conducted to (a) assess effectiveness of these measures on codeine prescribing in the "real-world" setting and (b) test feasibility of a study using a common protocol by regulators with access to databases. METHODS: The study was performed using BIFAP (Spain), CPRD (UK), and IMS® Disease Analyzer (France and Germany) databases. Prescribers included general practitioners (GPs) (France and UK), GPs and paediatricians together (Spain), and GPs, paediatricians, and ear, nose, and throat (ENT) specialists separately (Germany). Between January 2010 and June 2015, prevalence of codeine prescribing was obtained every 6 months, and a time series analysis (joinpoint) was performed. Codeine prescribing within ±30 days of TA was also identified. Furthermore, doses, durations, and prior prescribing of other analgesics were investigated. RESULTS: Over the 5-year period, codeine prescribing decreased in children younger than 12 years (by 84% in France and Spain, 44% in GP practices in Germany, and 33% in the United Kingdom). The temporal pattern was compatible with the regulatory intervention in France and the United Kingdom, whereas a decrease throughout the study period was seen in Germany and Spain. Decreased prescribing associated with TA was suggested in ENT practices in Germany. CONCLUSIONS: Codeine prescribing for children decreased in line with introduced regulatory measures. Multidatabase studies assessing impact of measures by EU regulators are feasible.

A randomized, double-blind study to assess the optimal duration of doxycycline treatment for human brucellosis.

BACKGROUND: Human brucellosis is usually treated with a combination of tetracyclines and aminoglycosides. However, the optimal duration of therapy has not been clearly determined. METHODS: We conducted a prospective, double-blind, randomized, multicenter study comparing treatment with doxycycline (100 mg po b.i.d.) for 30 days (30-day group) with the same dosage of doxycycline for 45 days (45-day group) in patients with brucellosis without endocarditis, spondylitis, or neurobrucellosis. All patients were treated with gentamicin (240 mg im once daily) for the first 7 days. Therapeutic outcome was evaluated by measuring relapse rates and drug safety. RESULTS: Seventy-three patients were included in each group. During the first 45 days after treatment, the percentage of patients with relapse was significantly higher in the 30-day group than in the 45-day group (12.3% vs. 1.37%; relative risk, 9.00; 95% confidence interval [CI], 1.17-69.2; P=.017). Between day 45 after treatment and 12 months after treatment, no further significant differences were found in relapse rates between groups (9.38% in the 30-day group vs. 11.11% in the 45-day group; relative risk, 0.84; 95% CI, 0.31-2.30; P=.78). Overall, relapses occurred in 15 (20.55%) of 73 patients in the 30-day group and in 9 (12.33%) of 73 patients in the 45-day group (relative risk, 1.67; 95% CI, 0.78-3.56; P=.264). Compliance and adverse effects were comparable in the 2 groups. CONCLUSIONS: Doxycycline treatment for 45 days significantly decreased early relapse rates among adults with brucellosis without increasing adverse effects.

Evaluación de dos pautas de quimioprofilaxis tuberculosa en pacientes infectados por el virus de la inmunodeficiencia humana / Assessment of two chemoprophylaxis regimens for tuberculosis in HIV-infected patients

Objetivo: Evaluar la cumplimentación, tolerancia y eficacia de una pauta corta de quimioprofilaxis para tuberculosis con isoniacida y rifampicina durante 3 meses frente a una pauta estándar de isoniacida durante 12 meses en pacientes con infección por el virus de la inmunodeficiencia humana (VIH). Pacientes y métodos: Ensayo clínico prospectivo, comparativo, aleatorizado y abierto realizado en cuatro hospitales generales y un centro penitenciario de Castilla-La Mancha. La profilaxis se administró en pacientes PPD positivos y pacientes anérgicos de acuerdo con las normas de los Centers for Diseases Control (CDC) de 1991. Los pacientes se distribuyeron de forma aleatoria en dos pautas: pauta de rifampicina a los que se les administraron 300 mg/día de isoniacida y 600 mg/día de rifampicina durante 3 meses, y pauta de isoniacida a los que se les administraron 300 mg/día de isoniacida durante 12 meses. Resultados: Se incluyeron 133 pacientes: 64 en la pauta isoniacida y 69 en la pauta rifampicina. Se toleró mejor la pauta de rifampicina, con un 28 por ciento de efectos adversos frente a un 55 por ciento en la pauta de isoniacida. La hepatotoxicidad fue más frecuente en la pauta de isoniacida, con un riesgo relativo (RR) de 2,2 (intervalo de confianza [IC] del 95 por ciento, 1,23-4,01). La hepatotoxicidad grave, que obligó a suspender el tratamiento, se relacionó con el tiempo de administración del fármaco, siendo más frecuente en la pauta de 12 meses. Se cumplimentó mejor la pauta corta, pero sin diferencias valorables. La incidencia de tuberculosis fue de 4,23 casos por 100 personas-año para la pauta de isoniacida y 2,08 para la pauta de rifampicina, con un riesgo relativo para desarrollar tuberculosis con la pauta de rifampicina de 0,51 (IC del 95 por ciento, 0,09-2,8) frente a la pauta de isoniacida, no estadísticamente significativo. La estancia en prisión se asoció con un riesgo significativo de tuberculosis, independientemente de la pauta de tratamiento (RR = 9,2; IC del 95 por ciento; 1,06-80,2). Conclusiones: En pacientes con infección por el VIH con PPD positivo o anérgicos, la pauta de rifampicina es al menos igual de eficaz para prevenir el desarrollo de tuberculosis que la pauta de isoniacida, y presenta menos efectos adversos (AU)