Generic drugs in Spain: price competition vs. moral hazard

This paper examines competition between generic and brand-name drugs in the regulated Spanish pharmaceutical market. A nested logit demand model is specified for the three most consumed therapeutic subgroups in Spain: statins (anticholesterol), selective serotonin reuptake inhibitors (antidepressants) and proton pump inhibitors (antiulcers). The model is estimated with instrumental variables from a panel of monthly prescription data from 1999 to 2005. The dataset distinguishes between three different levels of patients’ copayments within the prescriptions and the results show that the greater the level of insurance that the patient has (and therefore the lower the patient’s copayment), the lower the proportion of generic prescriptions made by physicians. It seems that the low level of copayment has delayed the penetration of generics into the Spanish market. Additionally, the estimation of the demand model suggests that the substitution rules and promotional efforts associated with the reference pricing system have increased generic market share, and that being among the first generic entrants has an additional positive effect.

Zinc Sulphate in the Treatment of Cutaneous Leishmaniasis: an in Vitro and Animal Study

This study was designed to evaluate the effectiveness of zinc sulphate both in vitro and in an animal model against both strains of old world cutaneous leishmaniasis. The in vitro sensitivities of promastigotes and axenic amastigotes of both Leishmania major and L. tropica to zinc sulphate was determined, the LD50 calculated and compared to the standard treatment for cutaneous leishmaniasis pentavalent antimony compounds. The results show that the two forms of both strains were sensitive to zinc sulphate and their respective LD50 were lower compared to the pentavalent antimony compound. Furthermore the sensitivities of the forms of both strains were tested using a simple slide method and compared to results of the standard method. To confirm this result, zinc sulphate was administered orally to mice infected with cutaneous leishmaniasis both therapeutically and prophylactically. Results showed that oral zinc sulphate was effective in both treatment and prophylaxis for cutaneous leishmaniasis. These results encourage the use of oral zinc sulphate in the treatment of cutaneous leishmaniasis clinically.

A single LC-tandem mass spectrometry method for the simultaneous determination of 14 antimalarial drugs and their metabolites in human plasma.

Among the various determinants of treatment response, the achievement of sufficient blood levels is essential for curing malaria. For helping us at improving our current understanding of antimalarial drugs pharmacokinetics, efficacy and toxicity, we have developed a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) requiring 200mul of plasma for the simultaneous determination of 14 antimalarial drugs and their metabolites which are the components of the current first-line combination treatments for malaria (artemether, artesunate, dihydroartemisinin, amodiaquine, N-desethyl-amodiaquine, lumefantrine, desbutyl-lumefantrine, piperaquine, pyronaridine, mefloquine, chloroquine, quinine, pyrimethamine and sulfadoxine). Plasma is purified by a combination of protein precipitation, evaporation and reconstitution in methanol/ammonium formate 20mM (pH 4.0) 1:1. Reverse-phase chromatographic separation of antimalarial drugs is obtained using a gradient elution of 20mM ammonium formate and acetonitrile both containing 0.5% formic acid, followed by rinsing and re-equilibration to the initial solvent composition up to 21min. Analyte quantification, using matrix-matched calibration samples, is performed by electro-spray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection in the positive mode. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effect variability, overall process efficiency, standard addition experiments as well as antimalarials short- and long-term stability in plasma. The reactivity of endoperoxide-containing antimalarials in the presence of hemolysis was tested both in vitro and on malaria patients samples. With this method, signal intensity of artemisinin decreased by about 20% in the presence of 0.2% hemolysed red-blood cells in plasma, whereas its derivatives were essentially not affected. The method is precise (inter-day CV%: 3.1-12.6%) and sensitive (lower limits of quantification 0.15-3.0 and 0.75-5ng/ml for basic/neutral antimalarials and artemisinin derivatives, respectively). This is the first broad-range LC-MS/MS assay covering the currently in-use antimalarials. It is an improvement over previous methods in terms of convenience (a single extraction procedure for 14 major antimalarials and metabolites reducing significantly the analytical time), sensitivity, selectivity and throughput. While its main limitation is investment costs for the equipment, plasma samples can be collected in the field and kept at 4 degrees C for up to 48h before storage at -80 degrees C. It is suited to detecting the presence of drug in subjects for screening purposes and quantifying drug exposure after treatment. It may contribute to filling the current knowledge gaps in the pharmacokinetics/pharmacodynamics relationships of antimalarials and better define the therapeutic dose ranges in different patient populations.

Neuro-developmental follow-up of neonates treated with magnesium sulfate for persistent pulmonary hypertension

Rapport de synthèse : DEVENIR NEURO-DEVELOPPEMENTAL DE NOUVEAU-NES TRAITES PAR DU SULFATE DE MAGNESIUM POUR UNE HYPERTENSION PULMONAIRE PERSISTANTE L'hypertension pulmonaire persistante du nouveau-né (HTPP) est un trouble de l'adaptation post-natale de la circulation pulmonaire caractérisé par une défaillance de la diminution normale des résistances vasculaires pulmonaires, accompagné d'un shunt droite-gauche, résultant en une hypoxémie profonde. C'est une pathologie sévère nécessitant des soins intensifs avec un risque augmenté de handicaps neurologiques chez les survivants. Le traitement de l'HTPP du nouveau-né inclut une ventilation mécanique ainsi que différents agents pharmacologiques pour dilater les vaisseaux pulmonaires, dont le sulfate de magnésium (MgSO4) à hautes doses par voie intraveineuse et le monoxyde d'azote par voie inhalée (iN0). Le MgSO4 est une alternative thérapeutique de l'HTPP du nouveau-né avec peu d'effets secondaires et une mortalité basse. Il a aussi été démontré que le MgSO4 est un traitement de l'HTPP du nouveau-né autant efficace que le iN0 et moins coüteux. Des études sur le suivi neuro-développemental de nouveau-nés avec HTPP traités selon différentes méthodes ont été publiées reportant des taux élevés de handicaps majeurs et mineurs. Plus récemment, des études de suivi après traitement par iN0 ont montré des taux plus bas qu'avec des traitements antérieurs. Le devenir neuro-développemental àlong terme d'enfants traités avec du MgSO4 n'a pas été documenté. Le but de cette étude est de décrire le développement des enfants qui ont présenté une HTPP traitée seulement avec du MgS04, de reporter l'incidence de handicaps majeurs et mineurs, et de les comparer à un groupe contrôle d'enfants sains du même âge ainsi qu'aux données de la littérature. La population consiste en 33 nouveau-nés traités pour une HTPP avec seulement du MgSO4 (groupe étude) et 32 nouveau-nés à terme sains (groupe contrôle). Un suivi neurodéveloppemental standardisé et approfondi a été effectué aux âges clés de 18 mois et 5 ans. Les taux de handicaps majeurs à 18 mois et 5 ans dans le groupe étude étaient de 6% et 11,4% respectivement, et de 0% aux deux âges dans le groupe contrôle. Les taux de handicaps mineurs aux mêmes âges étaient de 3% et 26,9% pour le groupe étude, et de 0% et 26,1% pour le groupe contrôle. Les quotients développementaux moyens à 18 mois étaient de 106,6 (DS 1,6) dans le groupe étude et de 118,3 (DS 1,0) dans le groupe contrôle (P < 0,001). L'index général intellectuel en âge préscolaire était de 112.6 (DS 3.7), respectivement de 119.3 (DS 3.1 ), sans différence significative entre les deux groupes. A 18 mois, les taux de handicaps majeurs et mineurs dans les groupes études et contrôle étaient de 6% et 3%. Dans la littérature, des taux entre 0% et 33% ont été décrits. A cet âge, il y avait une différence significative pour tous les scores du test de Griffiths, mëme en tenant compte du status socio-économique de la famille. Ceci suggère un léger retard du développement global et non une altération spécifique. Ces différences n'étaient plus significatives en âge préscolaire, suggérant un rattrapage développemental. Le taux de handicaps majeurs en âge préscolaire pour le groupe étude était de 11.5%, sans aucune infirmité motrice cérébrale. Ces résultats correspondent à ceux d'études de suivi après d'autres traitements jusqu'à l'âge de 24 mois avec des taux variant de 0% à 15%. Le taux de handicaps mineurs était de 26.9% dans le groupe étude et de 26.1% dans le groupe contrôle, sans différence significative entre les deux groupes. L'incidence de handicaps mineurs dans le groupe étude était plutôt élevée en comparaison aux données de la littérature (6 à 22% à 6 ans). Une explication possible est que nous avons considéré des problèmes de langage et de comportement comme handicaps mineurs. Ceci suggère une différence méthodologique et non une plus mauvaise issue dans nos deux groupes. Les évaluations cognitives des enfants des deux groupes se trouvaient dans la norme, ce qui est aussi le cas dans la littérature. En conclusion, cette étude longitudinale non randomisée d'enfants traités avec du MgSO4 seul pour une HTPP sévère ne montre pas de conséquences sur le devenir neuro-développemental à long terme. Cette étude le démontre pour la première fois. Malgré le fait que iN0 soit le traitement actuellement recommandé pour l'HTPP du nopuveau-né, le MgSO4 reste largement utilisé, en particulier dans des pays en voie de développement. L'absence de complications neuro-développementales majeures à long terme permet de considérer l'administration du MgSO4 pour le traitement de l'HTPP du nouveau-né en cas de non réponse ou d'inaccessibilité au iNO.

IPH response to Phase 2 of the New Strategic Direction for Alcohol and Drugs 2011-2016 (Northern Ireland)

The IPH response to the New Strategic Direction for Alcohol and Drugs questionnaire which has been designed to help stakeholders respond to New Strategic Direction for Alcohol and Drugs Phase 2 (2011-2016) consultation document.

Swallowing difficulties with oral drugs among polypharmacy patients attending community pharmacies.

Background Swallowing difficulties are common and can affect patients' ability to take solid oral dosage forms, thus compromising medication adherence. Strategies developed by patients to overcome such difficulties while taking medicines have seldom been described. Objective To determine prevalence and characteristics of swallowing difficulties among primary care patients attending their community pharmacies; to explore strategies developed by patients to overcome their difficulties, and health professionals' awareness of these problems. Setting Prospective study with a semi-structured questionnaire in random community pharmacies located in two Swiss regions. Method In each pharmacy, an interviewer asked 16 questions to each consecutive patient (18 years and older) with a prescription for at least 3 different solid oral forms. Main outcome measure Quantification of number of patients with swallowing difficulties and detailed description of difficulties. Results Among 122 pharmacies, 59 (48 %) accepted to join the study and 410 patients were enrolled. Thirty-seven patients (9.0 %) reported ongoing swallowing difficulties, while 55 patients (13.4 %) reported past difficulties. For the majority of patients, difficulties occurred at each single dose (83.7 %), with a single medication (59.8 %) and lasted for less than 12 months (53.8 %). Number of tablets was not the main trigger. Swallowing difficulties impaired extremely daily life in 12 % of the patients. Intentional non adherence (23 % of patients) and altering the oral dose formulation were the most common and potentially harmful strategies used by patients to overcome their swallowing difficulties. According to the patients, pharmacists and physicians rarely inquired about their swallowing difficulties. Conclusion We report a fairly high prevalence of swallowing difficulties in polypharmacy patients attending their community pharmacies. Pharmacists have to interview patients on their swallowing difficulties in a more systematic way, support patients in finding solutions and refer them to their physician if necessary to ensure continuity in care.

New Strategic Direction for Alcohol and Drugs 2006-2011 (NI) - Consultation response

The Institute of Public Health in Ireland welcomes the opportunity to comment on the consultation paper on the New Strategic Direction for Alcohol and Drugs 2006-2011 (NSD). We particularly welcome the approach taken in the strategy, which, from the conceptual base of the Programme Logic Approach, is firmly based on desired outcomes and the pathways leading to them. The Institute aims to improve health in Ireland, North and South by working to combat health inequalities and influence public policies in favour of health. The Institute applies a holistic model of health which emphasises a wide range of social determinants, including economic, environmental, social and biological factors, as well as the health and social services. The Institute’s work is based on the premise that improving health and reducing health inequalities can only be achieved through addressing these broader determinants of health.

New Strategic Direction for Alcohol & Drugs Phase 2 Second Update Report (June 2014) (PDF 1MB)

This second annual report provides an update of progress against the outcomes and indicators set out in NSD Phase 2.

New Strategic Direction for Alcohol and Drugs Phase 2 Update Report (March 2013) (PDF 652KB)

Update Report on NSD for Alcohol and Drugs Phase 2 - March 2013

New Strategic Direction for Alcohol and Drugs Phase 2 (2011-2016) - (December 2011) (PDF 886 KB)

New Strategic Direction for Alcohol and Drugs Phase 2 (2011-2016) - A framework for Reducing Alcohol and Drug Related Harm in Northern Ireland (December 2011)

New Strategic Direction for Alcohol & Drugs 2006-2011- NSD Update (April 2010) (PDF 611KB)

An update on the implementation and delivery of the New Strategic Direction on Alcohol and Drugs 2006-2011 (NSD)