Detection and chemical profiling of medicine counterfeits by Raman spectroscopy and chemometrics

Raman spectroscopy combined with chemometrics has recently become a widespread technique for the analysis of pharmaceutical solid forms. The application presented in this paper is the investigation of counterfeit medicines. This increasingly serious issue involves networks that are an integral part of industrialized organized crime. Efficient analytical tools are consequently required to fight against it. Quick and reliable authentication means are needed to allow the deployment of measures from the company and the authorities. For this purpose a method in two steps has been implemented here. The first step enables the identification of pharmaceutical tablets and capsules and the detection of their counterfeits. A nonlinear classification method, the Support Vector Machines (SVM), is computed together with a correlation with the database and the detection of Active Pharmaceutical Ingredient (API) peaks in the suspect product. If a counterfeit is detected, the second step allows its chemical profiling among former counterfeits in a forensic intelligence perspective. For this second step a classification based on Principal Component Analysis (PCA) and correlation distance measurements is applied to the Raman spectra of the counterfeits.

Medication exposure during pregnancy: a pilot pharmacovigilance system using health and demographic surveillance platform.

BACKGROUND: There is limited safety information on most drugs used during pregnancy. This is especially true for medication against tropical diseases because pharmacovigilance systems are not much developed in these settings. The aim of the present study was to demonstrate feasibility of using Health and Demographic Surveillance System (HDSS) as a platform to monitor drug safety in pregnancy. METHODS: Pregnant women with gestational age below 20 weeks were recruited from Reproductive and Child Health (RCH) clinics or from monthly house visits carried out for the HDSS. A structured questionnaire was used to interview pregnant women. Participants were followed on monthly basis to record any new drug used as well as pregnancy outcome. RESULTS: 1089 pregnant women were recruited; 994 (91.3%) completed the follow-up until delivery. 98% women reported to have taken at least one medication during pregnancy, mainly those used in antenatal programmes. Other most reported drugs were analgesics (24%), antibiotics (17%), and antimalarial (15%), excluding IPTp. Artemether-lumefantrine (AL) was the most used antimalarial for treating illness by nearly 3/4 compared to other groups of malaria drugs. Overall, antimalarial and antibiotic exposures in pregnancy were not significantly associated with adverse pregnancy outcome. Iron and folic acid supplementation were associated with decreased risk of miscarriage/stillbirth (OR 0.1; 0.08 - 0.3). CONCLUSION: Almost all women were exposed to medication during pregnancy. Exposure to iron and folic acid had a beneficial effect on pregnancy outcome. HDSS proved to be a useful platform to establish a reliable pharmacovigilance system in resource-limited countries. Widening drug safety information is essential to facilitate evidence based risk-benefit decision for treatment during pregnancy, a major challenge with newly marketed medicines.

Itsehoitolääkkeiden jakelukanavaverkoston laajentuminen Suomessa

Tutkielman tavoitteena oli tutkia itsehoitolääkkeiden jakelukanavaverkoston laajentumista Suomessa. Päätavoitteena oli löytää erilaisia tulevaisuuden toimintamalleja, ja tutkia, onko jakelun vapauttaminen uhka vai mahdollisuus lääketeollisuudelle. Lisäksi tutkielmassa oli tavoitteena selvittää millaisia erityisvaatimuksia itsehoitolääkkeiden jakeluunliittyy ja mitkä tekijät puoltavat ja mitkä jarruttavat itsehoitolääkkeiden kilpailun vapauttamista Suomessa. Tutkielma jakautuu teoreettiseen ja empiiriseen osaan. Teoreettinen osa keskittyy tarkastelemaan jakelukanaverkoston laajentumista lääketeollisuudessa. Empiirinen tutkimus toteutettiin laadullisena case-tutkimuksena ja tutkimusmenetelmänä käytettiin puoli-strukturoitua haastattelua. Tutkimustulokset osoittavat, että itsehoitolääkkeiden jakelun vapauttaminen on monitahoinen kysymys jamielipiteet sen tarpeellisuudesta ja hyödyllisyydestä vaihtelevat suuresti lääketeollisuuden jakelukanavan eri jäsenten välillä. Itsehoitolääkkeiden vähittäisjakelu voitaisiin tulevaisuudessa järjestää mahdollisesti joko vain apteekeista, tai apteekeista ja päivittäistavarakapoista. Mahdollisuutena olisi myös saada itsehoitolääkkeitä hotelleista ja ravintoloista, huoltamoista ja kioskeista. Lääkkeitä voisi ostaa myös erilaisista automaateista ja internetistä. Uudet kaupan muodot olisivat mahdollisia jos itsehoitolääkkeiden jakelu vapautuu tulevaisuudessa.

Phytochemical investigation of plants used in African traditional medicine: "Dioscorea sylvatica" (Dioscoreaceae), "Urginea altissima" (Liliaceae), "Jamesbrittenia fodina" and "Jamesbrittenia elegantissima" (Scrophulariaceae)

Les plantes médicinales représentent la seule source de médicaments pour près de 90 % de la population de certains pays d?Afrique. Le savoir-faire des guérisseurs traditionnels, d?une valeur inestimable, représente un point de départ pour l?investigation pharmacologique et phytochimique de ces médicaments naturels. Dans le cadre de ce travail, nous nous sommes dans un premier temps intéressés à valider l?utilisation en médecine traditionnelle de deux plantes, Diuscorea sylvatica (Dioscoreaceae) et Urginea altissima (Liliaceae), qui produisent, lorsqu?elles sont frottées sur la peau, une inflammation et des démangeaisons. Ces réactions cutanées ont pu être expliquées, au moins en partie, par la présence d?aiguilles acérées d?oxalate de calcium dans les organes souterrains. Ces microtraumatismes répétés de l?épiderme risquent de provoquer, lors d?une utilisation prolongée, des lésions granulomateuses. L?histamine n?a pas été détectée, mais d?autres substances pourraient être impliquées dans le processus inflammatoire. La seconde partie de ce travail a consisté en la détection, l?isolement et la caractérisation de nouveaux composés naturels présentant un intérêt thérapeutique potentiel. 70 extraits provenant de 28 plantes supérieures du Zimbabwe ont été soumis à un criblage chimique et biologique. Les extraits méthanoliques des parties aériennes de Jamesbrittenia fodina et J. elegantissima (Scrophulariaceae) ont été sélectionnés sur la base de leurs nombreuses activités. Le fractionnement guidé par l?activité de J. fudina a permis l?isolement des saponines A et B, responsables des activités antifongique, antibactérienne et molluscicide de l?extrait. De plus, les deux saponines ont montré une activité équivalente en tant qu?inhibiteurs de l?acétylcholinestérase, propriété encore non décrite pour cette classe de composés. Une analyse LC/uv/MS de l?extrait a permis d?attribuer l?activité antiradicalaire au verbascoside, un dérivé du phenylpropane; cette analyse a de plus montré la présence d?une série de dérivés de l?acide cinnamique, dont l?isolement a été entrepris. Deux problèmes d?instabilité sont apparus, empêchant l?isolement des composés par des méthodes chromatographiques de pointe, en dépit de très bonnes conditions de séparations. Des analyses LC/?H-NMR combinées à des analyses RMN classiques des mélanges ont permis d?attribuer ces instabilités d?une part à une isomérisation cis/trans induite par la lumière, et d?autre part à une transacylation du groupe cinnamoyl sur une unité de sucre. Ceci a permis l?identification de 12 esters cinnamiques d?iridoïdes, dont 8 nouveaux produits naturels. Ces dérivés présentent un intérêt thérapeutique, car des composés similaires ont montré des propriétés anti-inflammatoires significatives dans différents modèles in vivo. Deux flavanones ont aussi été isolées de l?extrait. Cette classe de composés n?a jamais été rapportée chez un membre des Scrophulariaceae. Une analyse LC/UV/MS comparative des extraits polaires des deux espèces, J. fodina et J. elegantissima, a été effectuée pour détecter la présence éventuelle de compos.és communs. Les saponines A et B et le verbascoside ont été identifiés dans l?extrait de J. elegantissima. Trois flavonoïdes ont de plus été isolés de ce dernier par CPC et HPLC semi-préparative.<br/><br/>In certain African countries, medicinal plants represent the unique source of to 90% of the population. The knowledge of traditional healers represents a basis for the pharmacological and phytochemical investigation of these natural medicines. This work first focused on the validation of use of two plants frequently employed in traditional medicine, Dioscorea sylvatica (Dioscoreaceae) and Urginea altissimu (Liliaceae), which produce mild inflammation and itching when rubbed on the skin. These cutaneous reactions were shown to be due, at least in part, to the presence of sharp needles of calcium oxalate, implying the risk of granulomatous lesions following a long term use. Histamine was not detected, but other compounds could be involved in the inflammatory process. The second part of this work consisted of the detection, isolation and characterisation of new natural compounds of potential therapeutic interest from African plants. Seventy extracts obtained from 28 higher plants of Zimbabwe were submitted to a chemical and biological screening. The methanol extracts of the whole plants of Jamesbrittenia fodina and J. elegantissima (Scrophulariaceae) were selected for their various activities. An activity-guided fractionation of J. fodina led to the isolation of the saponins A and B, responsible for the antifungal, antibacterial and molluscicidal properties. Both saponins were equally active as inhibitors of acetylcholinesterase, a property that has, to our knowledge, never been described for this class of compounds. A LC/UV/MS analysis of the extract allowed the identification of verbascoside as the product with radical scavenging activity, and indicated the presence of a series of potentially interesting cinnamic acid derivatives. Two types of instability problems occurred in the course of their isolation, as some compounds could not be separated despite very good chromatographic conditions. LC/'H-NMR analyses combined with in-mixture NMR analyses enabled the attribution of the cause of the instability in one case to a cidtrans light-induced isomerisation, and in the other case to a transacylation of the cinnamoyl moiety on a sugar residue. These problems of instability have not been the object of previous studies. 12 cinnamic iridoid esters could be characterised, 8 of these being new natural compounds. Several similar substances have displayed significant anti-inflammatory properties in different in vivo models, suggesting a therapeutic interest for these new derivatives. Two flavanones were isolated from the same extract. This class of compound has not been previously reported from species of the Scrophulariaceae family. A comparative LCAJVNS study of the polar extracts of the two species J. elegantissima and J. fodina was performed in order to detect possible common compounds. Saponins A and B and verbascoside were thus identified in .J. elegantissima. Moreover, three supplementary flavonoids were isolated from J. elegantissima..

Patterns and factors associated with low adherence to psychotropic medications during pregnancy-a cross-sectional, multinational web-based study.

BACKGROUND: No previous studies have explored how closely women follow their psychotropic drug regimens during pregnancy. This study aimed to explore patterns of and factors associated with low adherence to psychotropic medication during pregnancy. METHODS: Multinational web-based study was performed in 18 countries in Europe, North America, and Australia. Uniform data collection was ensured via an electronic questionnaire. Pregnant women were eligible to participate. Adherence was measured via the 8-item Morisky Medication Adherence Scale (MMAS-8). The Beliefs about Prescribed Medicines Questionnaire (BMQ-specific), the Edinburgh Postnatal Depression Scale (EPDS), and a numeric rating scale were utilized to measure women's beliefs, depressive symptoms, and antidepressant risk perception, respectively. Participants reporting use of psychotropic medication during pregnancy (n = 160) were included in the analysis. RESULTS: On the basis of the MMAS-8, 78 of 160 women (48.8%, 95% CI: 41.1-56.4%) demonstrated low adherence during pregnancy. The rates of low adherence were 51.3% for medication for anxiety, 47.2% for depression, and 42.9% for other psychiatric disorders. Smoking during pregnancy, elevated antidepressant risk perception (risk≥6), and depressive symptoms were associated with a significant 3.9-, 2.3-, and 2.5-fold increased likelihood of low medication adherence, respectively. Women on psychotropic polytherapy were less likely to demonstrate low adherence. The belief that the benefit of pharmacotherapy outweighed the risks positively correlated (r = .282) with higher medication adherence. CONCLUSIONS: Approximately one of two pregnant women using psychotropic medication demonstrated low adherence in pregnancy. Life-style factors, risk perception, depressive symptoms, and individual beliefs are important factors related to adherence to psychotropic medication in pregnancy.

Go-to-market strategy with pharmacies

The purpose of the research is to develop a go-to-market strategy with pharmacies. As it was agreed with the client of the study, Reckitt Benckiser, the focus is solely on non-prescription products. Therefore, prescription medicines are not considered in the study. The main objective of the research is to clarify consumer and pharmacy personnel behavior concerning non-prescription products. These issues are observed with surveys, which are provided to consumers and pharmacy personnel. The go-to-market strategy is based on the survey results and is comprised by utilizing the marketing-mix model. Legislation and the present state & trends are additional minor research problems of the study. The results of the research provide many descriptive insights about consumer and pharmacy personnel behavior. It is concluded that the consumers’ level of involvement with non-prescription products is low and the type of behavior is habitual. It is also demonstrated that several decision-making criteria are very different among different age groups and genders. Concerning pharmacy personnel, the factors that they base their product recommendations are revealed. In addition, the sources of medicine information for both consumers and pharmacy personnel are found out.

Mefloquine at the crossroads? Implications for malaria chemoprophylaxis in Europe.

Since its introduction to the market in 1985, mefloquine has been used for malaria chemoprophylaxis by more than 35 million travellers. In Europe, in 2014, the European Medicines Agency (EMA) issued recommendations on strengthened warnings, prescribing checklists and updates to the product information of mefloquine. Some malaria prevention advisors question the scientific basis for the restrictions and suggest that this cost-effective, anti-malarial drug will be displaced as a first-line anti-malaria medication with the result that vulnerable groups such as VFR and long-term travellers, pregnant travellers and young children are left without a suitable alternative chemoprophylaxis. This commentary looks at the current position of mefloquine prescribing and the rationale of the new EMA recommendations and restrictions. It also describes the new recommendations for malaria prophylaxis that have been adapted by Switzerland, Germany, Austria and Italy where chemoprophylaxis use is restricted to high-risk malaria-endemic areas.

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The contribution of biodiversity and ecosystem services to our health care needs is significant, both for the development of modern pharmaceuticals (Chivian and Bernstein 2008; Newmann and Cragg 2007; see also chapter on contribution of biodiversity to pharmaceuticals in this volume) and for their uses in traditional medicine (WHO 2013). Long before the rise of pharmaceutical development, societies have been drawing on their traditional knowledge, skills and customary practices, using various resources provided to them by nature to prevent, diagnose and treat health problems. Today, these practices continue to inform health-care delivery at the level of local communities in many places around the world (WHO 2013). In socioecological contexts such as these, several resources used for food, cultural and spiritual purposes are also used as medicines (Unnikrishnan and Suneetha 2012). Traditional medicine practices provide more than health care to these communities; they are considered a way of life and are founded on endogenous strengths, including knowledge, skills and capabilities.

Asociación de síndrome de boca ardiente con xerostomía y medicamentos

Objetivo: Identificar factores de riesgo para el síndrome de boca ardiente (SBA) a través de estudio de casos y controles. Material y métodos: Se realizó análisis cuantitativo del flujo salival total en reposo y estimulado; se registraron la xerostomía subjetiva, el consumo de medicamentos y los estados psicológicos de ansiedad y depresión en 40 pacientes con SBA y 40 controles. Resultados: El análisis ANOVA mostró diferencias significativas en las medias del número de medicamentos/día, número de medicamentos xerostomizantes/día, xerostomía subjetiva, ansiedad y depresión, entre los grupos estudiados. No se observaron diferencias significativas en las tasas de flujo salival en reposo y estimulado. El análisis de asociación Odds ratio determinó asociación del SBA con xerostomía y con el consumo de hipotensores y diuréticos. Conclusiones: Según los resultados de este estudio, se puede afirmar que el consumo de hipotensores y diuréticos fue un factor de riesgo para el padecimiento del SBA. La función de las glándulas salivales en los pacientes con SBA no está deteriorada.

Use of alternative and complementary therapies in labor and delivery care: a cross-sectional study of midwives" training in Catalan hospitals accredited as centers for normal birth

Background: The use of complementary and alternative medicine (CAM) and complementary and alternative therapies (CAT) during pregnancy is increasing. Scientific evidence for CAM and CAT in the field of obstetrics mainly covers pain relief in labor. Midwives are responsible for labor and delivery care: hence, their knowledge of CAM and CAT is important. The aims of this study are to describe the professional profile of midwives who provide care for natural childbirth in Catalan hospitals accredited as centers for normal birth, to assess midwives" level of training in CAT and their use of these therapies, and to identify specific resources for CAT in labor wards. Methods: A descriptive, cross-sectional, quantitative method was used to assess the level of training and use of CAT by midwives working at 28 hospitals in Catalonia, Spain, accredited as public normal birth centers. Results: Just under a third of midwives (30.4%) trained in CAT after completion of basic training. They trained in an average of 5.97 therapies (SD 3.56). The number of CAT in which the midwives were trained correlated negatively with age (r = - 0.284; p < 0.001) and with their time working at the hospital in years (r = - 0.136; p = 0.036). Midwives trained in CAT considered that the following therapies were useful or very useful for pain relief during labor and delivery: relaxation techniques (64.3%), hydrotherapy (84.8%) and the application of compresses to the perineum (75.9%). The availability of resources for providing CAT during normal birth care varied widely from center to center. Conclusions: Age may influence attitudes towards training. It is important to increase the number of midwives trained in CAM for pain relief during childbirth, in order to promote the use of CAT and ensure efficiency and safety. CAT resources at accredited hospitals providing normal childbirth care should also be standardized.

Use of alternative and complementary therapies in labor and delivery care: a cross-sectional study of midwives" training in Catalan hospitals accredited as centers for normal birth

Background: The use of complementary and alternative medicine (CAM) and complementary and alternative therapies (CAT) during pregnancy is increasing. Scientific evidence for CAM and CAT in the field of obstetrics mainly covers pain relief in labor. Midwives are responsible for labor and delivery care: hence, their knowledge of CAM and CAT is important. The aims of this study are to describe the professional profile of midwives who provide care for natural childbirth in Catalan hospitals accredited as centers for normal birth, to assess midwives" level of training in CAT and their use of these therapies, and to identify specific resources for CAT in labor wards. Methods: A descriptive, cross-sectional, quantitative method was used to assess the level of training and use of CAT by midwives working at 28 hospitals in Catalonia, Spain, accredited as public normal birth centers. Results: Just under a third of midwives (30.4%) trained in CAT after completion of basic training. They trained in an average of 5.97 therapies (SD 3.56). The number of CAT in which the midwives were trained correlated negatively with age (r = - 0.284; p < 0.001) and with their time working at the hospital in years (r = - 0.136; p = 0.036). Midwives trained in CAT considered that the following therapies were useful or very useful for pain relief during labor and delivery: relaxation techniques (64.3%), hydrotherapy (84.8%) and the application of compresses to the perineum (75.9%). The availability of resources for providing CAT during normal birth care varied widely from center to center. Conclusions: Age may influence attitudes towards training. It is important to increase the number of midwives trained in CAM for pain relief during childbirth, in order to promote the use of CAT and ensure efficiency and safety. CAT resources at accredited hospitals providing normal childbirth care should also be standardized.

Managing the Sick Child in the Era of Declining Malaria Transmission: Development of ALMANACH, an Electronic Algorithm for Appropriate Use of Antimicrobials.

OBJECTIVE: To review the available knowledge on epidemiology and diagnoses of acute infections in children aged 2 to 59 months in primary care setting and develop an electronic algorithm for the Integrated Management of Childhood Illness to reach optimal clinical outcome and rational use of medicines. METHODS: A structured literature review in Medline, Embase and the Cochrane Database of Systematic Review (CDRS) looked for available estimations of diseases prevalence in outpatients aged 2-59 months, and for available evidence on i) accuracy of clinical predictors, and ii) performance of point-of-care tests for targeted diseases. A new algorithm for the management of childhood illness (ALMANACH) was designed based on evidence retrieved and results of a study on etiologies of fever in Tanzanian children outpatients. FINDINGS: The major changes in ALMANACH compared to IMCI (2008 version) are the following: i) assessment of 10 danger signs, ii) classification of non-severe children into febrile and non-febrile illness, the latter receiving no antibiotics, iii) classification of pneumonia based on a respiratory rate threshold of 50 assessed twice for febrile children 12-59 months; iv) malaria rapid diagnostic test performed for all febrile children. In the absence of identified source of fever at the end of the assessment, v) urine dipstick performed for febrile children <2 years to consider urinary tract infection, vi) classification of 'possible typhoid' for febrile children >2 years with abdominal tenderness; and lastly vii) classification of 'likely viral infection' in case of negative results. CONCLUSION: This smartphone-run algorithm based on new evidence and two point-of-care tests should improve the quality of care of <5 year children and lead to more rational use of antimicrobials.

Situación actual de las Terapias Complementarias en España en el Grado de Enfermería

Objetivo: Describir la situación actual de las Terapias Complementarias en la formación enfermera en las escuelas y facultades de enfermería en España. Método: estudio observacional descriptivo transversal. Población de estudio todas las facultades, escuelas públicas y adscritas de España. Recolección de datos mediante una ficha de observación. Unidades de análisis los Planes de Estudio. Variables (créditos, tipo de asignatura, ubicación, tipo de terapia). Análisis descriptivo de los datos relativos y absolutos mediante hoja de Excel. Resultados:en la mayoría de las facultades y escuelas escrutadas la asignatura de Terapias Complementarias ha desaparecido y en aquellas que aparece es una asignatura optativa.Conclusión: la formación en Terapias Complementarias en España es deficiente, debido a que no se recoge como asignatura troncal y/o obligatoria. La ausencia de las Terapias Complementarias en el currículum, plantea interrogantes tales cómo el valor de éstas en la formación, conceptualización que tienen los docentes, la repercusión en la calidad de los cuidados, la formación de los docentes encargados de impartir la asignatura, así como el número de créditos y el curso a impartir en la titulación del Grado.

Synthesis of Janus compounds for the recognition of G-U mismatched nucleobase pairs

The design and synthesis of two Janus-type heterocycles with the capacity to simultaneously recognize guanine and uracyl in G-U mismatched pairs through complementary hydrogen bond pairing is described. Both compounds were conveniently functionalized with a carboxylic function and efficiently attached to a tripeptide sequence by using solid-phase methodologies. Ligands based on the derivatization of such Janus compounds with a small aminoglycoside, neamine, and its guanidinylated analogue have been synthesized, and their interaction with Tau RNA has been investigated by using several biophysical techniques, including UV-monitored melting curves, fluorescence titration experiments, and 1H NMR. The overall results indicated that Janus-neamine/guanidinoneamine showed some preference for the +3 mutated RNA sequence associated with the development of some tauopathies, although preliminary NMR studies have not confirmed binding to G-U pairs. Moreover, a good correlation has been found between the RNA binding affinity of such Janus-containing ligands and their ability to stabilize this secondary structure upon complexation.

Formación y aplicación de las terapias complementarias en los cuidados de enfermería al paciente oncológico

Objetivo general: Analizar la formación de las enfermeras y la aplicación de las terapias complementarias (TC) en los cuidados de enfermería al paciente oncológico. Ámbito de estudio: El estudio se realizó en el hospital Duran i Reynals de l"Hospitalet de Llobregat, en las unidades de: hematología clínica, terapia intensiva, tratamiento programado, hospital de día, oncología médica, cuidados paliativos, consultas externas, soporte de la atención continuada, servicio de oncología radioterápica y en el equipo de soporte hospitalario. Diseño: Estudio descriptivo transversal. Método: Aplicación de un cuestionario elaborado que consta de dos apartados, uno de datos demográficos y otro apartado con 8 preguntas especificas. Participantes: Enfermeras del área asistencial de todos los turnos que trabajen en las unidades mencionadas. Análisis de datos: Para el análisis de los datos se ha utilizado el paquete estadístico SPSS15.0 para Windows y se ha realizado un análisis descriptivo para todas las variables. Variables cualitativas: frecuencias y porcentajes. Variables cuantitativas: medidas de tendencia central y de dispersión. Resultados: El 58,8% de las enfermeras ha realizado algún tipo de formación en TC. Las intervenciones mente-cuerpo son las más efectuadas en cuanto a formación, seguidas de las terapias manuales y las terapias de base energética. La relajación-visualización es la terapia que más aplican las enfermeras oncológicas. Conclusiones: La formación de las enfermeras oncológicas en las TC es fundamental para poder informar y asesorar a sus pacientes y poder cuidarlos de una forma más holística. La falta de tiempo y de disposición del hospital al reconocimiento y valor de las TC son los principales factores de dificultad que se encuentran las enfermeras oncológicas.