Class of 2010 Abstract / OBJECTIVES: This is a selective systematic review of the methods used to monitor for the ocular adverse effects of chronic hydroxychloroquine use. This was done to describe the screening methods for detecting retinal toxicity and the recommendations for early detection of hydroxychloroquine associated retinopathy. METHODS: A literature search of OVID-MEDLINE and the Evidence Based Medicine (EBM) search database in the AHSL website were performed for the date range October 1999 to October 2009. Articles were selected based on content related to our purpose statement. Each article must have had at least one or more ophthalmic screening test including: fundus photography, Amsler grid, perimetry, color vision, and multifocal electroretinography. RESULTS: The search results returned a total of 67 articles. A total of twelve articles were selected for review. A total of 959 human subjects were studied and 22 patients had reported retinal changes attributed to hydroxychloroquine. Nine of the eleven studies that included mfERG recommended this specific test for monitoring for hydroxychloroquine induced retinopathy. Only six of the studies recommended the frequency of testing. The most common recommendation was to test at baseline and then at least annually. CONCLUSIONS: The results suggest the mfERG is the most sensitive and objective exam for early documentation of toxic retinopathy. In addition baseline and annual testing was suggested most often. The data also suggest that high risk patients be followed more closely as the most severe and irreversible damage occurs in this population.

No description available.

[ES] La presencia de residuos de antibióticos en la leche y los productos derivados representa un riesgo para los consumidores. Límites Máximos de Residuos (LMRs) no se han fijado para los productos lácteos y la transferencia de antibióticos de la leche a la cuajada y al lactosuero durante el proceso de elaboración del queso apenas ha sido estudiada. El objetivo de esta tesis fue evaluar la transferencia de antibióticos de la leche al queso y lactosuero, así como la validación de las características de varios métodos de cribado para la detección de antibióticos en muestras de suero de leche. En el primer estudio, el objetivo fue validar un método UHPLC-HRMS multi-residuo utilizando el analizador Orbitrap ExactiveTM, para el cribado cuantitativo de antibióticos en muestras de leche, queso fresco y lactosuero de acuerdo con los criterios especificados en la Decisión 657/2002/CE de la Comisión. El estudio de distribución mediante el método UHPLC-HRMS indicó que la mayor parte de antibióticos se transfirieron principalmente de la leche a la fracción lactosuero (hasta el 85,9%) durante la elaboración de queso. Por tanto, los porcentajes de retención de antibióticos en la cuajada fueron inferiores al 50%, excepto en el caso del ceftiofur (59,7%) y la dicloxacilina (52,8%), y muy variables entre los distintos antimicrobianos. En la mayor parte de los casos, la distribución de medicamentos no se vio afectada por la concentración de antibióticos presente en la leche, y estuvo escasamente relacionada con la lipofilicidad de los antibióticos. En el segundo estudio, se evaluaron las características de diferentes métodos de detección de antibióticos en muestras de lactosuero de acuerdo con la Decisión 657/2002/CE de la Comisión. En primer lugar, la especificidad (porcentaje de falsos positivos) y la capacidad de detección (CCß) del método de detección de inhibidores Eclipse Farm provisto del dispositivo e-Reader y de los métodos de unión a receptores 3Aminosensor, Quinosensor, Twinsensor y Tylosensor se evaluaron en muestras de lactosuero de leche de cabras, obteniendo en general, resultados similares a los obtenidos cuando se aplican para el análisis de la leche. También se evaluaron tres bioensayos en placa microtiter y respuesta dicotómica, que contenían Bacillus subtilis, Geobacillus thermocatenulatus y Geobacillus thermoleovorans, respectivamente, para ser aplicados simultáneamente con los métodos comerciales basados en la utilización de Geobacillus. stearothermophilus var. calidolactis. Elevados valores de especificidad (98-100%) se obtuvieron cuando las muestras de lactosuero fueron tratadas térmicamente (85ºC, 10 min). Bacillus subtilis, con menores valores de CCß para quinolonas y macrólidos, fue la opción más interesante para mejorar el perfil de detección del Eclipse 100. En cuanto al sistema multiplaca Screening Test for Antibiotic Residues (STAR) que utiliza cinco microorganismos diferentes (Geobacillus stearothermophilus para betalactámicos y sulfonamidas, Bacillus subtilis para aminoglucósidos, Kocuria varians para macrólidos, Escherichia coli para quinolonas y Bacillus cereus para tetraciclinas) aplicado al lactosuero, presentó una elevada especificidad (>=98%) en la mayor parte de casos. Los valores de CCß obtenidos con el protocolo STAR en muestras de lactosuero superan el LMR establecido en la leche, aunque podría representar una adecuada herramienta en la etapa de post-cribado y reducir el número de muestras destinadas al análisis cuantitativo por LC-MS/MS. La producción de queso a partir de leche con antibióticos genera residuos en el lactosuero. Por tanto, adecuados métodos de cribado para la detección de residuos de antibióticos en este importante subproducto de la elaboración del queso permitirían el establecimiento de una apropiada estrategia de control para prevenir la presencia de antibióticos en el lactosuero y, así, evitar los posibles efectos / [CA] La presència de residus d'antibiòtics en la llet i els productes derivats representa un risc per a la salut del consumidor. Límits Màxims de Residus (LMRs) no s'han fixat per als productes lactis i la transferència d'antibiòtics de la llet al formatge i al sèrum durant el procés d'elaboració del formatge quasi no s'ha estudiat. L'objectiu d'aquesta tesi va ser avaluar la transferència d'antibiòtics de la llet a les fraccions formatge i sèrum, així com la validació de la resposta de diversos mètodes per a la detecció d'antibiòtics en mostres de sèrum de llet. En el primer estudi, l'objectiu va ser validar un mètode UHPLC-HRMS multi-residu utilitzant l'analitzador Orbitrap ExactiveTM, per al garbellat quantitatiu d'antibiòtics en mostres de llet, formatge fresc i sèrum, d'acord amb els criteris especificats en la Decisió 657/2002/CE de la Comissió. L'estudi de partició utilitzant UHPLC-HRMS mètode va indicar que la major part d'antibiòtics es van transferir principalment de la llet a la fracció sèrum de llet (fins al 85,9%) durant l'elaboració de formatge. Per tant, els percentatges de retenció d'antibiòtics en la quallada van ser inferiors al 50%, excepte en el cas del ceftiofur (59,7%) i la dicloxacilina (52,8%), i molt variables entre els diferents fàrmacs. En la majoria dels casos, la distribució de medicaments no es va veure afectada per la concentració d'antibiòtics present en la llet per a la producció de formatge, i va estar escassament relacionada amb la lipofilicitat dels antibiòtics. En el segon estudi, es van avaluar les característiques de diferents mètodes de detecció d'antibiòtics en mostres de sèrum d'acord amb la Decisió 657/2002/CE de la Comissió. L'especificitat (percentatge de falsos positius) i la capacitat de detecció (CCß) d'una prova d'inhibició microbiana (Eclipse Farm acoblat al dispositiu e-Reader) i d'assajos d'unió a receptors (3Aminosensor, Quinosensor, Twinsensor i Tylosensor) es van avaluar en mostres de sèrum de llet de cabra, obtenint en general, resultats similars als obtinguts quan s'apliquen per a l'anàlisi de la llet. Es van avaluar tres bioassatjos en placa microtiter i resposta dicotòmica, que contenien Bacillus subtilis, Geobacillus thermocatenulatus i Geobacillus thermoleovorans, respectivament, per a ser aplicats simultàniament amb els mètodes comercials basats en la utilització de Geobacillus stearothermophilus var. calidolactis. Elevats valors d'especificitat (98-100%) es van obtindre quan les mostres de sèrum van ser tractades tèrmicament (85°C, 10 min). Bacillus subtilis, amb menors valors de CCß per a quinolones i macròlids, va ser l'opció més interessant per a millorar el perfil de detecció del mètode Eclipse 100. Respecte al sistema multiplaca Screening Test for Antibiotic Residues (STAR) que utilitza cinc microorganismes diferents (Geobacillus stearothermophilus per a betalactàmics i sulfonamides, Bacillus subtilis per a aminoglucòsids, Kocuria varians per a macròlids, Escherichia coli per a quinolones i Bacillus cereus per a tetraciclines), va presentar una elevada especificitat (>=98%) en la major part de casos. Els valors de CCß obtinguts amb el protocol STAR en mostres de sèrum superen el LMR establit en llet. No obstant això, aquest mètode podria convertir-se en una eina adequada en el post-garbellament per a la identificació preliminar dels residus d'antibiòtics presents en el sèrum de llet i reduir el nombre de mostres destinades a l'anàlisi quantitativa per LC-MS/MS, que és un mètode més complex i car. La producció de formatge a partir de llet amb antibiòtics genera residus en el sèrum. L'adequada prestació dels mètodes de garbellat per a la detecció de residus d'antibiòtics en aquest subproducte d'elaboració del formatge permetria l'establiment d'una estratègia de control per a evitar el risc derivat de la presència d'aquestes substàncies en el sèrum, amb efectes negatius sobre la / [EN] The presence of antibiotic residues in milk and dairy products poses a risk for consumer health, mainly the development of antimicrobial resistance. Maximum Residue Limits (MRLs) for veterinary drugs have not been established for dairy products. Furthermore, the transfer of antibiotics from milk to cheese and whey fractions during cheese-making has been scarcely studied and, therefore, the impact of the use of whey containing antibiotics for the manufacture of foodstuffs for human and animal consumption is unknown. The aim of this thesis was to evaluate the transfer of antibiotics from milk to cheese and whey fractions, as well as the validation of the performance of several methods to screen antibiotics in whey samples. In the first study, a multiresidue UHPLC-HRMS method using the Orbitrap ExactiveTM analyser for the quantitative screening of antibiotics in milk, fresh cheese, and whey samples was validated according to Commission Decision 2002/657/EC, using samples from three different dairy matrices (milk, fresh cheese and whey) from cows, sheep and goats. The partitioning study by UHPLC-HRMS method indicated that most antibiotics were mainly transferred from milk to whey fraction (up to 85.9%) during cheese-making. Thus, retention rates in the rennet curd fraction were lower than 50%, except for ceftiofur (59.7%) and dicloxacillin (52.8%), and very variable between drugs. In most cases, drug distribution was unaffected by the antibiotic concentration present in milk for cheese production and was poorly related to the drug lipophilicity. In the second study, the performance of different methods for screening antibiotics in whey samples was evaluated in accordance with Commission Decision 2002/657/EC, by conducting three experiments focused on commercially available screening tests, microtiter plate bioassays, and a semi-quantitative multi-plate system, respectively. Specificity (false-positive rate) and Detection Capability (CCß) of a microbial inhibitor test (Eclipse Farm coupled to e-Reader device) and receptor-binding assays (3Aminosensor, Quinosensor, Twinsensor, and Tylosensor) were evaluated in whey samples from goats, having in general, similar results than those obtained when they are applied for milk analysis. Three microtiter plate bioassays with dichotomous response containing Bacillus subtilis, Geobacillus thermocatenulatus and Geobacillus thermoleovorans, respectively, were evaluated simultaneously with commercially available tests using Geobacillus stearothermophilus var calidolactis. High specificity values (>=98%) were obtained when whey samples were heat treated (85ºC, 10 min) prior to analysis. Bacillus subtilis, having lower CCß values for quinolones and macrolides, was the most interesting option to improve the detection profile of the Eclipse 100. Regarding the multiplate system Screening Test for Antibiotic Residues (STAR) using Geobacillus stearothermophilus for ß-lactams and sulfonamides, Bacillus subtilis for aminoglycosides, Kocuria varians for macrolides, Escherichia coli for quinolones and Bacillus cereus for tetracyclines, high specificity values (>=98%) were obtained in most cases. The CCß values obtained using the STAR protocol in whey samples exceed the MRL established in milk for most of the substances considered. However, this method could become an adequate tool in post-screening and reduce the number of samples destined for the quantitative analysis by LC-MS/MS, which is a more complex and expensive method. The production of cheese using milk containing antibiotics generates drug residues in whey. Thus, the suitable performance of screening methods for the detection of veterinary drug residues in this cheese-making by-product will allow the establishment of an adequate control strategy to prevent the presence of antibiotic residues in whey and to avoid the hazards associated to human and animal health and environment. / This research forms part of the Project AGL-2013-45147-R financed by the Ministerio de Ciencia e Innovación / Giraldo Gómez, J. (2020). Transfer of antibiotics from goat's milk to cheese and whey [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/155899

Background Pain and dysfunction in the temporomandibular region (Temporomandibular Disorders, TMD) are common conditions in the general population with an estimated treatment need of 5-15% in the general population. However, in Sweden, traceable performed treatments are significantly lower. The reasons for this indicated under-treatment are not known. To easily detect patients with a potential TMD related condition, three screening questions, 3Q/TMD, have been introduced. The aim with this project was to evaluate the validity and outcome of the 3Q/TMD with the objective to recognize individuals with TMD and potential treatment need in the Public Dental Health service (PDHS). Methods The thesis is based on four study samples; three from the PDHS in the county of Västerbotten, Sweden and one sample from the specialized orofacial pain clinic at the Academic Centre for Dentistry, ACTA, Amsterdam, the Netherlands. The bases for all studies are individuals’ answers to the 3Q/TMD and quantitative approaches were used in the analyses. The prevalence of affirmative answers was evaluated in a large cross-sectional study over the lifespan. The validity of the 3Q/TMD in relation to the Diagnostic Criteria for TMD (DC/TMD) as reference standard was established in two case-control studies. The outcome of the 3Q/TMD on TMD treatment within general practice was evaluated in a cohort study. Results Affirmative answers to the 3Q/TMD increased during adolescence. Women answered affirmatively to the 3Q/TMD significantly more often compared to men for all age groups expect for the first and last parts of a one hundred-year lifespan. The highest prevalence was reported by women during their fertile period in life. In a general population sample, 74% of individuals with an affirmative answer qualified for a DC/TMD pain or dysfunctional diagnosis, as compared to 64% in a specialist patient sample. In the general population sample, for the individual 3Q/TMD questions, as well as combinations of questions, the negative predictive values were high (0.92-0.99). For the specialist sample, when at least one question was answered affirmatively the negative predictive value was high (0.90). The positive predictive value was high (0.89) when all three questions were positive. There was significantly more treatment performed or recommended for 3Q-positives (21.5%) compared to 3Q-negatives (2.2%) (P<0.001). The odds ratio for TMD-related treatment for 3Q-positives versus 3Q-negatives was 12.1 (95% CI: 6.3-23.4). Conclusion The 3Q/TMD is a convenient and valid tool to recognize individuals who would benefit from a further TMD examination within an adult, general population. Within specialized orofacial pain clinics, the questions are useful as guidance for further diagnostics. Although the 3Q/TMD was a factor related to TMD treatment, the majority of individuals with self-reported symptoms of TMD still did not receive traceable assessment or treatment. Factors associated with dentists’ clinical decision-making in relation to TMD warrants further research. The utilization of the 3Q/TMD as a part of a decision tree for the clinician can improve the health care for patients with TMD and is therefore recommended within dentistry. / Bakgrund Smärta och funktionsstörningar i käksystemet (TMD) är vanligt förekommande och de flesta av dessa patienter kan behandlas framgångsrikt i tandvården. Tidigare studier har visat att det kan finnas en skillnad mellan det skattade vårdbehovet och utförd behandling för patienter med TMD i tandvården. Anledningen till detta är inte känt och har identifierats som en kunskapslucka av Socialstyrelsen. Den vanligaste orsaken till akut smärta i ansiktsregion är tandvärk medan kronisk smärta oftast är relaterat till smärttillstånd i muskulatur och käkled (TMD). Att leva med smärta har en negativ påverkan på livskvaliteten oavsett om smärtan är orsakad av tandvärk eller TMD. Kvinnor uppger symtom på TMD ungefär två gånger så ofta som män och förekomsten är som högst bland kvinnor i arbetsför ålder. Smärtan är ofta relaterad till stress och långvarig smärta ökar risken för såväl spridning till andra lokalisationer som till sömnbesvär och nedstämdhet. Tidig intervention har visat sig betydelsefull för att minska risken för negativa konsekvenser relaterat till kroniska besvär. Sammantaget visar detta på vikten av ett system inom tandvården för att tidigt identifiera patienter som är i möjligt behov av fördjupad utredning och eventuellt behandling. Därför har tre screeningfrågor för TMD, 3Q/TMD införts inom tandvården. I Folktandvården i Västerbotten infördes frågorna i maj 2010 som en obligatorisk del av den digitala hälsodeklarationen för samtliga patienter. Syfte Syftet med avhandlingen har varit att synliggöra patienter med smärta och käkfunktionsstörning i befolkningen och att därmed förbättra omhändertagandet av patienter med TMD inom Folktandvården. De specifika målen var att: i) beskriva förekomst av frekvent smärta och dysfunktion i ansikte, käke och käkled för män och kvinnor för olika åldersgrupper baserat på tre screeningfrågor ii) bedöma de tre screeningfrågornas validitet i förhållande till en diagnos enligt Diagnostic Criteria for TMD, DC/TMD i två olika populationer iii) utvärdera utfallet av 3Q/TMD på klinisk beslutsprocess inom Folktandvården i Västerbotten, Sverige. Studiepopulation och metod Avhandlingen baserades på fyra olika urval av patientpopulationer, tre från Folktandvården i Västerbotten, Sverige och en från Specialistkliniken från Academish Centrum Tandheelkunde Amsterdam, ACTA, Amsterdam, Nederländerna. Underlaget för samtliga studier var baserade på individuella svar på de tre screeningfrågorna. Förekomsten av de som svarat ja på någon av frågorna utvärderades i en tvärsnittsstudie bland nästan 140 000 individer och över ett helt livsspann. Validiteten för 3Q/TMD i relation till en diagnos enligt DC/TMD utvärderades i två fall-kontroll studier. Först undersöktes en studiepopulation från Folktandvården i Västerbotten, Sverige för att representera allmän befolkningen. Därefter utvärderades screeningfrågorna bland de patienter som remitterats till en specialistklinik i Amsterdam, Nederländerna på grund av TMD relaterade besvär. Dessa representerar remitterade patienter. Utfallet av 3Q/TMD på TMD behandling i Folktandvården utvärderades i en prospektiv kohort studie. Resultat Förekomsten av de som svarat ja på någon av frågorna ökar under tonåren. Kvinnor svarar ja på någon av frågorna signifikant oftare än män i alla åldrar, utom i början och slutet av livsspannet. Den högsta prevalensen noterades för kvinnor i fertil ålder. I allmänbefolkningen kvalificerar 74% av de som svarat ja på någon av frågorna även för en DC/TMD diagnos. Motsvarande siffra för urvalet från specialistkliniken var 64%. I urvalet från allmänbefolkningen var det negativa prediktiva värdet högt för såväl alla enskilda frågor som för kombinationer av frågor (0.92-0.99). Bland de remitterade patienterna, var negativt prediktivt värde högt när individen svarade ja på minst en fråga (0.90). Positivt prediktivt värde var högt när individen svarat ja på alla tre frågorna (0.89). Behandling hade utförts eller rekommenderats signifikant oftare till de som svarat ja på någon av frågorna (21.5%) jämfört med de som svarat nej på alla tre frågor (2.2%) (P<0.001). Odds ratio för TMD behandling för 3Q-positiva jämfört med 3Q-negativa var 12.1 (95% CI:6.3-23.4). Slutsats Sammanfattningsvis visar resultaten att en betydande andel av befolkningen, framför allt kvinnor i arbetsför ålder, har smärta och/eller funktionsstörningar i käksystemet. Frågorna är lämpliga för att screena patienter i behov av en fördjupad utredning. De som svarat nej kommer med stor sannolikhet inte att kvalificera för en diagnos enligt DC/TMD. Bland remitterade patienter kommer majoriteten att svara ja på någon av frågorna. I allmäntandvården får två tredjedelar av det som svarat ja på minst en fråga, inte ett synliggjort omhändertagande baserat på vad som är angivet i deras tandvårdsjournal. Detta kan tyda på brister bland allmäntandläkare och tandhygienister i kliniskt beslutsfattande för patienter med TMD.

L’usage des antibiotiques en médecine vétérinaire peut entrainer la présence de résidus d’antibiotiques dans les denrées alimentaires d’origine animale. Ces résidus peuvent présenter des risques (eg. toxicologiques, allergies, antibiorésistance) pour la santé du consommateur. La fixation de limites réglementaires pour ces résidus et un contrôle adapté sont primordiaux pour garantir la sécurité des consommateurs. Les méthodes de dépistage sont utilisées en première intention et représentent donc l’étape critique du contrôle. La validation d’une méthode va permettre de garantir qu’elle est adaptée à l’usage souhaité, aux attentes réglementaires et attester de sa performance. La validation constitue une exigence normative (ie. ISO 17025) et réglementaire (ie. Décision européenne 2002/657/CE). Dans une première partie, la diversité des méthodes de dépistage est présentée. Les méthodes dites conventionnelles de type microbiologique ou immunologique, développées dans les années 1980, sont toujours couramment utilisées, en raison de leur faible coût. Des méthodes innovantes, appelées biocapteurs, sont constituées d’un biorécepteur (eg. anticorps, aptamère) et d’un transducteur (eg. électrochimique, optique, massique, calorimétrique) pour la détection du signal. Ces méthodes sont en développement permanent et les progrès technologiques permettent de développer des méthodes de plus en plus sensibles, portables, parfois économiques. Dans une deuxième partie, différentes approches de validation, sous forme de réglementations, de lignes directrices ou de normes, sont discutées. La validation d’une méthode comporte deux étapes : tout d’abord la caractérisation des performances, puis la validation proprement dite par rapport à des critères préétablis. Les approches peuvent être absolue (une seule méthode) ou relative (comparaison de méthodes), globale (combinaison de plusieurs caractéristiques en une seule) ou critère par critère. L’objet de cette thèse est de comparer ces différentes approches de validation, afin de statuer sur leur application possible aux différentes méthodes de dépistage des résidus et déterminer si leurs conclusions sont équivalentes ou non. Différentes approches ont été testées en les appliquant pour valider des méthodes de dépistage de différents types : conventionnelles microbiologique et immunologique, innovantes par biocapteurs optiques. L’approche par comparaison de méthodes n’est pas adaptée aux méthodes de dépistage des résidus d’antibiotiques. En effet, le choix de la méthode de référence est compliqué car il n’existe pas de méthodes normalisées. De plus, les méthodes de référence choisies ont souvent des principes très différents de la méthode alternative et sont le plus souvent moins performantes. L’approche globale, telle que la Probabilité de détection (POD) et le profil d’exactitude sont applicables aux méthodes de dépistage. Ces approches récentes sont de plus en plus utilisées dans d’autres domaines et présentent un intérêt à être développées pour les méthodes de dépistage des résidus d’antibiotiques. Enfin, l’approche critère par critère de la décision européenne 20002/657/CE et du guide de validation européen de 2010, couramment appliquée aux résidus d’antibiotiques, comporte une caractéristique majeure et une avancée dans la validation qui est la capacité de détection (CCβ). En conclusion, les méthodes de dépistage sont en constante évolution, grâce au développement des biocapteurs. L’amélioration de leurs performances permet de répondre de mieux en mieux à la problématique du contrôle des résidus d’antibiotiques dans les denrées alimentaires. La validation des méthodes est primordiale pour garantir un contrôle efficace. Nous avons pu observer l’évolution de la validation ces 20 dernières années, à travers les travaux de cette thèse. Cette évolution doit continuer et des perspectives d’évolution des référentiels de validation sont présentées dans cette thèse. / The use of antibiotic residues for animal treatment could lead to the presence of antibiotic residues in food of animal origin. The consumer could face some risks (eg. toxicological, allergies, bacterial resistance), due to these residues. The setting of regulatory limits or these residues and an adapted control of food products are thus essential to guarantee the safety of the consumers. Screening methods are used in first intention and represent the critical stage of the control. The validation of a method will guarantee that the method if fitted for purpose, adapted to the regulatory expectations and give evidence of its performance. The validation is mandatory due to international standards (ie. ISO 17025) and regulatory requirements (ie. European decision 2002/657/EC). In a first part, the diversity of screening methods is presented. The conventional methods, microbiological or immunological types, developed in the 1980s, are always used, because of their moderate cost. Innovative methods, called biosensors, consist of a bioreceptor (eg. antibody, aptamer) and a transducer (eg. electrochemical, optical, mass sensitive, calorimetric) for the detection of the signal. These methods are in continuous development and the technological progress allows developing more, more sensitive, portable and sometimes economic methods. In a second part, various approaches of validation, in the form of regulations, guidelines or standards, are discussed. The validation of a method contains two stages: first of all the characterization of the performances, then the validation itself with regard to preestablished criteria. The approaches can be absolute (a single method) or relative (comparison of methods), global (combination of several characteristics in only one) or criterion by criterion. The object of this thesis is to compare these various approaches of validation, to conclude on their potential application for different residue screening methods and to determine if their conclusions are equivalent or not. Various approaches have been tested by applying them to the validation of screening methods of various types: conventional methods (microbiological and immunological) and innovative optical biosensors. The approach by comparison of methods is not fitted to screening methods for antibiotic residues. Indeed, the choice of the reference method is complicated because there are no standardized methods. Furthermore, the chosen reference methods often have very different principles from the alternative method and are less sensitive most of the time. The global approach, such as the Probability of detection (POD) and the accuracy profile are applicable to the screening methods. These recent approaches are more and more used in other fields and present an interest to be developed for the screening methods for antibiotic residues. Finally, the criterion by criterion approach of the European decision 20002/657/EC and the European guideline for the validation of screening methods of 2010, usually applied to the screening methods for antibiotic residues, introduced a major characteristic and an improvement in the validation which is the detection capability (CCß). In conclusion, the screening methods are constantly evolving, thanks to the development of new biosensors. The improvement of their performances allows answering better and better to the issue of the control of antibiotic residues in foodstuffs. The validation of the methods is essential to guarantee an effective control. We were able to observe the evolution of the validation these last 20 years, through the works of this thesis. This evolution has to continue and perspectives of evolution of guidelines, regulations and standards of validation are presented in this thesis.

Although alcohol plays an important role in psychiatric morbidity, there is a general lack of strategies within psychiatric care to intervene at alcohol problems in an early stage (secondary prevention). The aim of this thesis was to increase knowledge of adequate forms of secondary alcohol prevention in psychiatric care.   The capacity of three brief screening instruments was investigated in a psychiatric outpatient sample (n=1811). The results indicate that the HED (heavy episodic drinking) screener, strongly recommended for health care settings, is not sufficiently sensitive in a psychiatric setting. Instead, the full AUDIT (Alcohol Use Disorders Identification Test) is recommended. The knowledge and attitudes of psychiatric staff members to problem-drinking patients were studied and the effects of a three-hour training course were investigated. Confidence in self-perceived capacity to intervene in more severe alcohol problems was raised among all staff after training. Awareness of early signs of problem drinking was raised among psychologists and social workers. The therapeutic attitude of the psychiatric staff was higher when compared with primary care staff. Two forms of brief intervention were delivered by clinical psychiatric staff. At 12 months, 29% of all participants had improved their drinking habits, moving from hazardous to non-hazardous level (21%) or from harmful to hazardous level (8%). In the improved group, mean AUDIT score was reduced from 11.0 points at baseline to 5.5 points. Differences in outcome between the two interventions could not be identified. Nine high-risk drinking young female psychiatric patients were interviewed, focusing on reasons for excessive drinking and factors facilitating a change in drinking habits. Alcohol played an important role in the lives of the young women. It made them feel social and helped them deal with unbearable emotions. It was also used as a means of self-harm, representing the first stage in an escalating self-harm process. They expressed a need for help from their caregivers in addressing the underlying reasons for drinking. Secondary alcohol prevention strategies including appropriate screening methods, staff training and the elaboration of tailored interventions are urgently needed in psychiatric care. The findings of this thesis can be used when forming such strategies.

Children's mental health problems are a significant public health concern. They are costly to society in both human and financial terms. This thesis contributes to the 'science of prevention' by examining issues related to the identification of children at risk of mental health problems. In particular, it was of interest to determine whether 'at-risk' children could be identified before the development of significant behavioural or emotional problems. Three areas were explored: family risk factors that predict the development of children's mental health problems, teachers' ability to identify family risk factors, and parent- and teacher-report screening methods. Data were collected from the parents and teachers of over 1000 children in preschool to Year 3 as part of the Promoting Adjustment in Schools (PROMAS) Project. Parents and teachers each completed two questionnaires at two time points, one year apart. Parents completed the Family Risk Factor Checklist - Parent (FRFCP) and the Child Behaviour Checklist (CBCL) and the equivalent instruments for teachers were, respectively, the Family Risk Factor Checklist - Teacher (FRFC-T) and the Teacher Report Form (TRF). The FRFC-P and FRFC-T were original to the current research and were designed to assess children's exposure to multiple family risk factors across five domains: adverse life events and instability (ALI), family structure and socioeconomic status (SES), parenting practices (PAR), parental verbal conflict and mood problems (VCM), and parental antisocial and psychotic behaviour (APB). Paper 1 investigated the psychometric properties of the FRFC-P and the potential for its use at a population-level to establish community risk factor profiles that subsequently inform intervention planning. The FRFC-P had satisfactory test-retest reliability and construct validity, but modest internal consistency. Risk assessed by the PAR domain was the most important determinant of mental health problem onset, while the PAR, VCM, and APB domains were the strongest predictors of mental health problem persistence. This risk factor profile suggests that, for the studied population, the largest preventive effects may be achieved through addressing parenting practices. Paper 2 examined teachers' knowledge of children's exposure to family risk factors using the FRFC-T. While teachers had accurate knowledge of children's exposure to risk factors within the ALI and SES domains, they had poor knowledge of children's exposure to risk factors within the PAR, VCM, or APB domains - the types of risk factors found in Paper 1 to be the most strongly related to children's mental health problems. Nevertheless, teachers' knowledge of children's exposure to risk factors within the ALI and SES domains predicted children's mental health problems at one year follow-up even after accounting for children's behaviour at the first assessment. Paper 3 investigated the potential of both the FRFC-P and FRFC-T for identifying individual, at-risk children. The accuracy of the FRFC in predicting internalising versus externalising disorders was compared against behavioural and simple nomination screening methods. For both parents and teachers, the behavioural screening methods were superior, however, the simple nomination method also showed promise for teachers. Both parents and teachers were more accurate at identifying children at risk of externalising mental health problems than children at risk of internalising problems. The performance of the FRFC and simple nomination methods in identifying children for selective interventions, before the development of significant behavioural or emotional problems, was also tested. Both the FRFC and simple nomination methods showed only modest predictive accuracy for these children. Combined, the results suggest that while on the one hand, the FRFC is useful for population level screening to inform intervention planning, on the other hand, it falls short of achieving good predictive accuracy for individual children. Future research should investigate ways to optimise predictive accuracy for individual children, particularly those at risk of developing internalising disorders. One option may be to use the FRFC in conjunction with behavioural screening methods. The challenge is to develop accurate screening methods that remain practical to complete at a population level. Finally, this body of research provides insight into the feasibility of offering selective preventive interventions within the school setting. While significant obstacles remain, there were several promising indications that using screening methods such as FRFC-T or simple nomination, teachers may be able to identify children earlier on the developmental pathway, before significant behavioural or emotional symptoms have developed.

Introdução: A triagem nutricional é um método utilizado mundialmente, para identificar indivíduos em risco nutricional, sendo os idosos o segmento populacional mais vulnerável. No entanto, no Brasil, ainda não existem métodos específicos para triagem nutricional de idosos domiciliados. Objetivos: i) identificar métodos de triagem nutricional para idosos domiciliados e selecionar o mais adequado para utilização no Brasil; ii) realizar a adaptação transcultural e validação de conteúdo do método selecionado; e iii) verificar as propriedades psicométricas de confiabilidade, de validade e de equivalência operacional do método selecionado. Métodos: Esta tese é composta por três manuscritos. O primeiro apresenta revisão sistemática de métodos de triagem nutricional para idosos domiciliados, publicados nas bases de dados PubMed, LILACS e Web of Science, no período de 1990 a 2012. O segundo descreve o processo de adaptação transcultural e validação de conteúdo do método selecionado, Determine Your Nutritional Health® (DNH), para o Brasil. O terceiro analisou a versão brasileira do método de triagem nutricional Verifique a condição nutricional do idoso, quanto à confiabilidade (pelo teste de McNemar e gráficos de Bland & Altman), à validade discriminante (pela correlação entre o resultado do escore final de triagem nutricional, com as variáveis antropométricas e indicadores nutricionais, utilizando o teste de Mann Whitney) e à equivalência operacional (pelos dados relativos à duração de realização do método e pelo grau de entendimento pela escala Likert entre 1 a 5 ). Resultados: Manuscrito 1: 12 métodos de triagem nutricional que atenderam aos critérios de elegibilidade foram descritos, segundo suas características, forma de identificação do risco nutricional, propriedades psicométricas e aspectos operacionais, sendo selecionado para adaptação transcultural para o Brasil, o método DNH. Manuscrito 2: Adaptações de palavras e expressões foram realizadas originando a versão brasileira Verifique a condição nutricional do idoso apresentando as mesmas questões da versão original do DNH, contudo, em formato mais claro, por meio de perguntas, consideradas acessíveis e de fácil entendimento. Manuscrito 3: Constatou-se que o método Verifique a condição nutricional do idoso é confiável, ou seja, foi capaz de reproduzir respostas semelhantes quando realizadas duas vezes (em momentos diferentes) no mesmo indivíduo, mostrou resultados suficientes quanto à validação discriminante e apresentou duração média da entrevista de 7 minutos, com nota média geral de entendimento de 4,8. Conclusões: O método de triagem nutricional DNH foi selecionado como o mais adequado para adaptação transcultural para o Brasil. Seu processo de adaptação resultou na versão brasileira Verifique a condição nutricional do idoso. Esse método mostrou-se confiável e apresentou resultados suficientes referentes à sua validade discriminante e equivalência operacional, constituindo uma alternativa preventiva para ser utilizada, por profissionais de saúde, com a finalidade de alertar os idosos, quanto à sua condição nutricional para procurarem ajuda especializada. / Background: The nutritional screening is a method used worldwide to identify individuals at nutritional risk, being the older people the most vulnerable population segment. However, in Brazil, there are still no specific methods for nutritional screening in older domiciled people. Objectives: i) identify nutritional screening methods for older domiciled people and select the most adequate for the use in Brazil; ii) carry out the cross-cultural adaptation and validation of content of the method selected; and iii) verify the psychometric properties of reliability, validity and operational equivalence of the method selected. Methods: This thesis is composed of three manuscripts. The first presents a systematic review of nutritional screening methods for the use in older domiciled people published in the databases PubMed, LILACS and Web of Science from 1990 to 2012. The second describes the process of cultural adaptation and validation of contents of the selected method, Determine Your Nutritional Health® (DNH) to Brazil. The third analyzed the Brazilian version of the nutritional screening method \"Verify the condition nutritional of the older people\", regarding the reliability (by the McNemar test and Bland & Altman), the discriminate validity (by correlation between the result of the final score of the screening nutrition, with the anthropometric variables and nutritional indicators, using the Mann-Whitney test) and operational equivalence (by data on the duration of implementation of the method and degree of understanding by Likert scale of 1-5). Results: Manuscript 1: 12 nutritional screening methods which attended the eligibility criteria were described, according to their characteristics, form of identification of nutritional risk, psychometric properties and operational aspects, being selected for cross-cultural adaptation to Brazil, the DNH method. Manuscript 2: Adaptations of words and expressions were made resulting in the Brazilian version of \"Verify the condition nutritional of the older people\", presenting the same issues of the original version of DNH, however, in clearer format, through questions considered accessible and easy to understand. Manuscript 3: It was found that the \"Verify the condition nutritional of the older people\" is reliable, that is, was able to reproduce similar responses when carried out twice (at different moments) with the same individual. It showed sufficient results regarding the discriminate validity and presented an average duration of 7 minutes to carry out the method, with a 4.8 general average grade of understanding. Conclusions: The nutritional screening method DNH was selected as the most adequate for cross-cultural adaptation to Brazil. Its adjustment process resulted in the Brazilian version of \"Verify the condition nutritional of the older people\". This method proved to be reliable and presented results sufficient regarding its discerning validity and operational equivalence, constituting a preventative alternative to be used by health professionals, with the purpose of alerting the older people about their nutritional condition to seek specialized help.

Introdução: A triagem nutricional é um método utilizado mundialmente, para identificar indivíduos em risco nutricional, sendo os idosos o segmento populacional mais vulnerável. No entanto, no Brasil, ainda não existem métodos específicos para triagem nutricional de idosos domiciliados. Objetivos: i) identificar métodos de triagem nutricional para idosos domiciliados e selecionar o mais adequado para utilização no Brasil; ii) realizar a adaptação transcultural e validação de conteúdo do método selecionado; e iii) verificar as propriedades psicométricas de confiabilidade, de validade e de equivalência operacional do método selecionado. Métodos: Esta tese é composta por três manuscritos. O primeiro apresenta revisão sistemática de métodos de triagem nutricional para idosos domiciliados, publicados nas bases de dados PubMed, LILACS e Web of Science, no período de 1990 a 2012. O segundo descreve o processo de adaptação transcultural e validação de conteúdo do método selecionado, Determine Your Nutritional Health® (DNH), para o Brasil. O terceiro analisou a versão brasileira do método de triagem nutricional Verifique a condição nutricional do idoso, quanto à confiabilidade (pelo teste de McNemar e gráficos de Bland & Altman), à validade discriminante (pela correlação entre o resultado do escore final de triagem nutricional, com as variáveis antropométricas e indicadores nutricionais, utilizando o teste de Mann Whitney) e à equivalência operacional (pelos dados relativos à duração de realização do método e pelo grau de entendimento pela escala Likert entre 1 a 5 ). Resultados: Manuscrito 1: 12 métodos de triagem nutricional que atenderam aos critérios de elegibilidade foram descritos, segundo suas características, forma de identificação do risco nutricional, propriedades psicométricas e aspectos operacionais, sendo selecionado para adaptação transcultural para o Brasil, o método DNH. Manuscrito 2: Adaptações de palavras e expressões foram realizadas originando a versão brasileira Verifique a condição nutricional do idoso apresentando as mesmas questões da versão original do DNH, contudo, em formato mais claro, por meio de perguntas, consideradas acessíveis e de fácil entendimento. Manuscrito 3: Constatou-se que o método Verifique a condição nutricional do idoso é confiável, ou seja, foi capaz de reproduzir respostas semelhantes quando realizadas duas vezes (em momentos diferentes) no mesmo indivíduo, mostrou resultados suficientes quanto à validação discriminante e apresentou duração média da entrevista de 7 minutos, com nota média geral de entendimento de 4,8. Conclusões: O método de triagem nutricional DNH foi selecionado como o mais adequado para adaptação transcultural para o Brasil. Seu processo de adaptação resultou na versão brasileira Verifique a condição nutricional do idoso. Esse método mostrou-se confiável e apresentou resultados suficientes referentes à sua validade discriminante e equivalência operacional, constituindo uma alternativa preventiva para ser utilizada, por profissionais de saúde, com a finalidade de alertar os idosos, quanto à sua condição nutricional para procurarem ajuda especializada. / Background: The nutritional screening is a method used worldwide to identify individuals at nutritional risk, being the older people the most vulnerable population segment. However, in Brazil, there are still no specific methods for nutritional screening in older domiciled people. Objectives: i) identify nutritional screening methods for older domiciled people and select the most adequate for the use in Brazil; ii) carry out the cross-cultural adaptation and validation of content of the method selected; and iii) verify the psychometric properties of reliability, validity and operational equivalence of the method selected. Methods: This thesis is composed of three manuscripts. The first presents a systematic review of nutritional screening methods for the use in older domiciled people published in the databases PubMed, LILACS and Web of Science from 1990 to 2012. The second describes the process of cultural adaptation and validation of contents of the selected method, Determine Your Nutritional Health® (DNH) to Brazil. The third analyzed the Brazilian version of the nutritional screening method \"Verify the condition nutritional of the older people\", regarding the reliability (by the McNemar test and Bland & Altman), the discriminate validity (by correlation between the result of the final score of the screening nutrition, with the anthropometric variables and nutritional indicators, using the Mann-Whitney test) and operational equivalence (by data on the duration of implementation of the method and degree of understanding by Likert scale of 1-5). Results: Manuscript 1: 12 nutritional screening methods which attended the eligibility criteria were described, according to their characteristics, form of identification of nutritional risk, psychometric properties and operational aspects, being selected for cross-cultural adaptation to Brazil, the DNH method. Manuscript 2: Adaptations of words and expressions were made resulting in the Brazilian version of \"Verify the condition nutritional of the older people\", presenting the same issues of the original version of DNH, however, in clearer format, through questions considered accessible and easy to understand. Manuscript 3: It was found that the \"Verify the condition nutritional of the older people\" is reliable, that is, was able to reproduce similar responses when carried out twice (at different moments) with the same individual. It showed sufficient results regarding the discriminate validity and presented an average duration of 7 minutes to carry out the method, with a 4.8 general average grade of understanding. Conclusions: The nutritional screening method DNH was selected as the most adequate for cross-cultural adaptation to Brazil. Its adjustment process resulted in the Brazilian version of \"Verify the condition nutritional of the older people\". This method proved to be reliable and presented results sufficient regarding its discerning validity and operational equivalence, constituting a preventative alternative to be used by health professionals, with the purpose of alerting the older people about their nutritional condition to seek specialized help.

Studiens syfte var att undersöka kriminalvårdens centrala riktlinjer för psykisk ohälsa bland anstaltsklienter och om dessa riktlinjer realiseras i praktiskt arbete på två olika avdelningar: normalavdelning och behandlingsavdelning på en anstalt av högsta säkerhetsklass i Sverige. Data samlades in genom intervjuer med åtta kriminalvårdare och en psykolog. Resultatet visade att psykisk ohälsa ur ett personalperspektiv är vanligt förekommande, främst ADHD, depression, ångest och sömnsvårigheter. Majoriteten av respondenterna visste inte om vilka riktlinjer som finns vid behandling av klienters psykiska ohälsa. Slutsatsen är att det råder brister i kommunikationen mellan ledningen och kriminalvårdarna inom anstalten. / The purpose of this study was to examine the correctional institutions central guidelines for mental problems among their clients and whether these guidelines are used in practical work within two different facilities: normal facilities and treatment facilities at an institution of a maximum security prison in Sweden. Data was collected through interviews with eight prison officers and a psychologist. The results showed that mental problems from a staff perspective are common, mainly ADHD, depression, anxiety and insomnia. The majority of the respondent did not have knowledge about the central guidelines for client’s mental problems. Conclusion is that there are deficiencies in communication between management and the prison officers within the correctional institution.