Abstract The ductus arteriosus connects the pulmonary artery and the descending aorta in the foetus. In normal neonatal transition, the ductus closes soon after birth. If the duct remains significantly open after birth, it may complicate the recovery of a very preterm infant. Present treatments of patent ductus arteriosus (PDA) are either medical (ibuprofen or indomethacin) or surgical (ligation). However, these treatments can have serious side effects, especially in the most immature infants. This doctoral thesis studied the potential role of intravenous paracetamol for PDA treatment in very preterm infants born before 32 weeks of gestation. Consequences of the PDA treatments in an epidemiological birth cohort were also studied. In retrospective Study I stated that treatments of PDA decreased after the introduction of IV paracetamol for early pain management in preterm infants. Study II showed in a randomised clinical trial for the first time that paracetamol has a biological effect on the ductus arteriosus in preterm infants soon after birth. The ductus closed significantly earlier in the paracetamol group than in the placebo group. The epidemiological cohort Study III showed evidence that both medical and surgical treatment of PDA associated with severe bronchopulmonary dysplasia in infants born very preterm. Additionally, surgical PDA ligation was associated with increased risk of necrotising enterocolitis and intraventricular haemorrhage. Study IV showed that treatment of PDA was not associated with increased mortality, even in the most immature preterm infants born before 28 weeks of gestation. / Tiivistelmä Valtimotiehyt on sikiöaikana avoimena oleva suoni, joka yhdistää keuhkovaltimon laskevaan aorttaan ja ohjaa vähähappisen veren istukkaan. Yhdessä soikean aukon kanssa suoni takaa sikiön verenkierron normaalin toiminnan ennen keuhkojen avautumista. Mikäli valtimotiehyt jää syntymän jälkeen pitkittyneesti auki, muuttaa se keskosen verenkiertoa siten, että osa aortan verenkiertoa ohjautuu keuhkoverenkiertoon vaikeuttaen pienen keskosen toipumista. Nykyhoitoina käytetään joko lääkkeellistä (ibuprofeeni tai indometasiini) tai kirurgista sulkua. Lääkkeellinen hoito ei ole kovin tehokas kaikista epäkypsimmillä keskosilla ja hoitoihin liittyy vakaviakin sivuvaikutuksia. Väitöskirjassa tutkittiin parasetamolilääkityksen vaikutusta hyvin pienen keskosen avoimen valtimotiehyen sulkeutumiseen. Epidemiologisessa osiossa tutkittiin nykyhoitojen sivuvaikutuksia hyvin pienillä keskosilla. Osatyössä I todettiin, että avoimen valtimotiehyen hoidon tarve väheni merkittävästi sen jälkeen kun parasetamoli oli otettu käyttöön kivun hoidossa vastasyntyneiden teholla. Osatyö II oli satunnaistettu ja sokkoutettu hoitotutkimus, jossa todettiin alkuperäishavaintona, että parasetamolilla on biologinen vaikutus keskosen avoimeen valtimotiehyeen. Parasetamolia saaneilla keskosilla valtimotiehyt sulkeutui aikaisemmin kuin verrokeilla. Hoidolla ei todettu merkittäviä sivuvaikutuksia. Osatöissä III ja IV tutkittiin kaikkien vuosina 2005−2013 Suomessa syntyneiden hyvin pienten keskosten avoimen valtimotiehyen hoitoja. Lääkehoidolla (ibuprofeeni ja indometasiini) ja kirurgisella hoidolla todettiin olevan yhteys keskosen kroonisen keuhkotaudin (BPD) vaikeimpaan muotoon. Kirurgisella hoidolla oli yhteys keskosen vaikeaan suolitulehdukseen ja vaikeaan aivoverenvuotoon. Kuolleisuuden riskin ei kuitenkaan todettu lisääntyneen valtimotiehyen hoitoihin liittyen.

Neste trabalho foram estudadas as potencialidades eletroanalíticas de um material híbrido condutor baseado em acetato de celulose e grafite com eletrodeposição de filme condutor de Azul da Prússia (CA/G/PB) como sensor para espécies com importância biológica. O material híbrido foi preparado pelo processo de inversão de fase e caracterizado pelas técnicas de microscopia eletrônica de varredura acoplada com espectroscopia de energia dispersiva (SEM-EDS) e voltametria cíclica. O composto Azul da Prússia (PB) foi imobilizado na superfície do material por eletropolimerização, aplicando-se um potencial fixo de 20 mV em uma janela de -0,3 V a 1,2 V. Os estudos eletroquímicos do eletrodo modificado CA/G/PB foram realizados em solução de KCl 0,1 mol.L-1, sendo obtidos dois pares redox para a espécie eletroativa imobilizada com potenciais médios (E0) em 0,204 V e 0,842 V, indicando um comportamento quase-reversível. O eletrodo demonstrou alta estabilidade após 500 ciclos redox, não sendo observada lixiviação da espécie eletroativa da superfície da matriz modificada. Os dois pares redox do material híbrido CA/G/PB permaneceram praticamente constantes entre os pH 5,0 e 8,0, indicando que as intensidades de pico não são significativamente afetadas nessa faixa de pH. A correlação linear entre as intensidades de pico e a raiz quadrada da velocidade de varredura, indicou que o sistema possui um comportamento similar aqueles em que o processo é controlado por difusão das espécies eletroativas à superfície do eletrodo. O azul da Prússia imobilizado foi aplicado na determinação de dopamina (DP), ácido úrico (AU), ácido ascórbico (AA) e Paracetamol (PCT) através da técnica de voltametria cíclica, voltametria de pulso diferencial e cronoamperometria. / In this work, we studied the electroanalytical potential of a conductive hybrid material based on cellulose acetate and graphite with electrodeposition Blue conductor film of Prussia (CA / G / PB) as a sensor for species with biological importance. The hybrid material was prepared by phase inversion process and characterized by the techniques of scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS) and cyclic voltammetry. The dye of Prussian blue (PB) was immobilized on the surface of the material by electropolymerization applying a fixed potential of 20 mV in a interval from -0.3 V to 1.2 V. The electrochemical behavior of the modified electrode CA / G / PB were performed in solution of 0.1 mol L-1 KCl being obtained two redox couples for the electroactive species immobilized with midpoint potentials (E0) in 0.204 V and 0.842 V, indicating a quasi-reversible behavior. The electrode showed high stability after 500 redox cycles with no observed leaching of electroactive species to the surface of the modified electrode. The two redox pair of the CA / G / PB electrode was kept practically constant within pH 5.0 and 8.0, indicating that the peak intensities are not significantly affected in this pH range. The linear correlation between peak intensities and the square root of scan rate, indicated that the system has a similar behavior those in which the process is controlled by diffusion of electroactive species to the electrode surface. The immobilized Prussian blue was applied to determine dopamine (DP), uric acid (UA), ascorbic acid (AA) and paracetamol (PCT) by analytical techniques of cyclic voltammetry, differential pulse voltammetry and chronoamperometry.

Neste trabalho foram estudadas as potencialidades eletroanalíticas de um material híbrido condutor baseado em acetato de celulose e grafite com eletrodeposição de filme condutor de Azul da Prússia (CA/G/PB) como sensor para espécies com importância biológica. O material híbrido foi preparado pelo processo de inversão de fase e caracterizado pelas técnicas de microscopia eletrônica de varredura acoplada com espectroscopia de energia dispersiva (SEM-EDS) e voltametria cíclica. O composto Azul da Prússia (PB) foi imobilizado na superfície do material por eletropolimerização, aplicando-se um potencial fixo de 20 mV em uma janela de -0,3 V a 1,2 V. Os estudos eletroquímicos do eletrodo modificado CA/G/PB foram realizados em solução de KCl 0,1 mol.L-1, sendo obtidos dois pares redox para a espécie eletroativa imobilizada com potenciais médios (E0) em 0,204 V e 0,842 V, indicando um comportamento quase-reversível. O eletrodo demonstrou alta estabilidade após 500 ciclos redox, não sendo observada lixiviação da espécie eletroativa da superfície da matriz modificada. Os dois pares redox do material híbrido CA/G/PB permaneceram praticamente constantes entre os pH 5,0 e 8,0, indicando que as intensidades de pico não são significativamente afetadas nessa faixa de pH. A correlação linear entre as intensidades de pico e a raiz quadrada da velocidade de varredura, indicou que o sistema possui um comportamento similar aqueles em que o processo é controlado por difusão das espécies eletroativas à superfície do eletrodo. O azul da Prússia imobilizado foi aplicado na determinação de dopamina (DP), ácido úrico (AU), ácido ascórbico (AA) e Paracetamol (PCT) através da técnica de voltametria cíclica, voltametria de pulso diferencial e cronoamperometria. / In this work, we studied the electroanalytical potential of a conductive hybrid material based on cellulose acetate and graphite with electrodeposition Blue conductor film of Prussia (CA / G / PB) as a sensor for species with biological importance. The hybrid material was prepared by phase inversion process and characterized by the techniques of scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS) and cyclic voltammetry. The dye of Prussian blue (PB) was immobilized on the surface of the material by electropolymerization applying a fixed potential of 20 mV in a interval from -0.3 V to 1.2 V. The electrochemical behavior of the modified electrode CA / G / PB were performed in solution of 0.1 mol L-1 KCl being obtained two redox couples for the electroactive species immobilized with midpoint potentials (E0) in 0.204 V and 0.842 V, indicating a quasi-reversible behavior. The electrode showed high stability after 500 redox cycles with no observed leaching of electroactive species to the surface of the modified electrode. The two redox pair of the CA / G / PB electrode was kept practically constant within pH 5.0 and 8.0, indicating that the peak intensities are not significantly affected in this pH range. The linear correlation between peak intensities and the square root of scan rate, indicated that the system has a similar behavior those in which the process is controlled by diffusion of electroactive species to the electrode surface. The immobilized Prussian blue was applied to determine dopamine (DP), uric acid (UA), ascorbic acid (AA) and paracetamol (PCT) by analytical techniques of cyclic voltammetry, differential pulse voltammetry and chronoamperometry.

Abstract The purpose of this study was to investigate the clinical implications of a combination of a peripheral opioid, paracetamol (APAP) and ketoprofen (KTP) on the intensity of acute postoperative pain by focusing on tonsillectomy (TE) and third molar extraction. A second focus in the study was to assess the utility of the surgical ultrasonically activated scalpel (HS) technique for TE. In Study I, TE was performed on one side using the HS and on the contralateral side using a “blunt dissection technique”. The first TE study (I) demonstrated that - based on NRS pain scores during the first 10 postoperative hours - intra-operative blood loss and need for haemostasis were greater on the blunt dissection side than on the HS side. Pain scores were higher on the HS side than on the cold dissection side during the second postoperative week. Study III assessed the analgesic effect of a peripheral dose of 4 mg morphine. The peritonsillar infiltration of morphine locally did not significantly decrease pain compared to the control side. Studies (II and IV) included patients who were scheduled for third molar extraction. In Study II, patients received 1000 mg APAP or 100 mg KTP or both or a placebo to evaluate pain relief after third molar extraction. This study demonstrated that the mean sum of pain intensity differences scores up to the 1.5 h mark and the mean time to onset of pain relief at rest and on swallowing were favoured in the combination group more than in the APAP, KTP, and placebo groups. In Study IV, patients were assigned for a submucosal injection of 2 mg morphine or NaCl into either the non-inflamed (Trial I) or the inflamed (Trial II) peridental tissue, while the active control group received the same drugs in reverse order intramuscular (IM). Postoperative pain intensity at rest and on swallowing was assessed in all studies using the numerical rating scale (NRS). Pain scores in the peripheral morphine group at rest (Trials I and II) and on swallowing (Trial I) were not associated with any further pain reduction. Pain scores on swallowing during the 2–6 hours postoperative period (Trial II) were greater in the IM morphine group. HS TE was associated with decreased pain in the early postoperative period, but there was increased pain and otalgia during the second postoperative week. Locally administered peripheral morphine was not associated with any benefit during the postoperative period after TE. The multimodal analgesia combination of a single dose of KTP and APAP demonstrated the same benefit during the early postoperative period without an increase in side effects. Locally administered peripheral morphine produced significant analgesia on swallowing during the early postoperative stage in inflamed tissue after third molar extraction. / Tiivistelmä Hyvä leikkauksen jälkeinen kivunhoito on yksilöllisesti suunniteltua, turvallista, helppokäyttöistä ja taloudellista. Nykyään pyritään kivunlievityksessä hyödyn-tämään eri vaikutuspaikkoihin kohdistuvia hoitoja eli multimodaalista kivun¬hoitoa. Tämän työn tarkoituksena oli selvittää eri kivunlievitysmenetelmien tehoa ja turvallisuutta kahdessa eri toimenpiteessä: nielurisojen poistoleikkauksen (TE) tai viisaudenhampaan poistoleikkauksen jälkeen. Tutkimuskokonaisuus käsittelee leikkaustekniikan (Ultraääniveitsi), lääke-ainekombinaatioiden ja perifeerisesti annostellun morfiinin vaikutusta post-operatiiviseen kipuun. Tutkimusaineisto koostuu neljästä tutkimuksesta. Kaikki työt olivat satunnaistettuja ja kaksoissokkoutettuja. Kipu mitattiin numeerista asteikolla (Numerical Rating Scale, NRS) sekä levossa että nielemisen aikana enintään 2 viikon ajan. Ultraääniveitsen käytön vaikutusta postoperatiiviseen kipuun verrattiin perinteiseen leikkaustekniikkaan. Potilailta toinen nielurisa poistettiin ultraääni¬veistä käyttäen ja toinen tylpästi irrotellen kylmiä instrumentteja käyttäen. Kipu oli perinteisellä tekniikalla leikatulla puolella voimakkaampi kuin ultraääni¬veitsellä leikatulla puolella leikkauspäivänä. Toisen leikkauksen jälkeisen viikon aikana kipu oli kuitenkin voimakkaampaa ultraääniveitsillä leikatulla puolella. Parasetamolin (APAP), ketoprofeenin (KTP) tuottamaa kivunlievitystä ja näiden yhteisvaikutusta verrattiin viisaudenhampaan poistoleikkauksen jälkeen. KTP ja APAP kombinaatio antoi tehokkaamman kivunlievityksen ja nopeamman hoitovasteen kuin kumpikaan lääke yksin annettuna. Perifeerisesti infiltroidun morfiinin vaikutusta kipuun tutkittiin TE sekä viisaudenhampaan poistoleikkauksen jälkeen. TE jälkeen toiselle puolelle infiltroitiin nielurisan taakse 4 mg morfiinia ja toiselle puolelle fysiologista suolaliuosta. Viisaudenhampaan poistoleikkauksessa paikallisesti infiltroitua 2 mg morfiinia verrattiin lihakseen annettuun samaa lääkkeeseen kahdessa eri tilanteessa, joko tulehtuneeseen tai tulehtumattomaan kudokseen annosteltuna. Paikallisesti infiltroidulla morfiinilla ei todettu kipua lievittävää vaikutusta TE jälkeen. Tulehtuneeseen kudokseen infiltroitu morfiini lievensi leikkauksen jälkeistä nielemiskipua 2–6 tuntia leikkauksesta. Tulehtumattomaan kudokseen infiltroidulla morfiinilla ei saatu lisäetua. Yhteenvetona voidaan todeta, että TE ja viisaudenhampaanpoistoleikkauksen jälkeen kivunhoitoa voidaan optimoida multimodaalisin kivunhoidon keinoin. Tutkimustulokset auttavat potilaskohtaisen yksilöllisen kivunhoidon suunnittelussa.

No / The surface energetic parameters of carbamazepine and paracetamol have been studied using inverse gas chromatography modified to produce dry and ambient conditions within the column. The values of the dispersive component of the surface free energy (¿DS) do not change significantly at the increased relative humidity. In contrast the specific component of the free energy of adsorption (-¿GSPA) as measured by polar probes, can either remain constant or decrease by up to 10%, depending on the material and the probe. This indicates that an increase in the relative humidity causes a decrease in the surface energetics of the powder surface. It is proposed that where the water molecules are adsorbing to the same sites as the polar probes, the interaction of these probes with the surface is decreased. To identify these sites, the preferential interaction of each probe, including water, with the drug molecule has been modelled.

Yes / Three dimensional printing (3DP) was used to engineer novel oral drug delivery devices, with specialised design configurations loaded with multiple actives, with applications in personalised medicine. A filament extruder was used to obtain drug-loaded - paracetamol (acetaminophen) or caffeine - filaments of polyvinyl alcohol with characteristics suitable for use in fused-deposition modelling 3D printing. A multi-nozzle 3D printer enabled fabrication of capsule-shaped solid devices, containing paracetamol and caffeine, with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different from the drug in the adjacent layers; and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least squares component matching to produce false colour representations of distribution of the drugs showed clearly the areas that contain paracetamol and caffeine, and that there is a definitive separation between the drug layers. Drug release tests in biorelevant media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both drugs was simultaneous and independent of drug solubility. With the DuoCaplet design it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device, and the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design configurations and unique drug release characteristics, which would not otherwise be possible using conventional manufacturing methods. / The full-text of this article will be released for public view at the end of the publisher embargo on 10 Oct 2016.

Revisión por pares

Some previously described environmental associations for atopic eczema may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level results for multiple atopic eczema risk factors. The International Study of Asthma and Allergies in Childhood (i.e, ISAAC) Phase Three surveyed children in schools (the sampling unit) regarding atopic eczema symptoms and potential risk factors. We assessed the effect of these risk factors on atopic eczema symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence. Overall, 546,348 children from 53 countries were included. At ages 6–7 years, the strongest individual-level associations were with current paracetamol use (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.37–1.54), which persisted at school-level (OR = 1.55, 95% CI = 1.10–2.21), early-life antibiotics (OR = 1.41, 95% CI = 1.34–1.48), and early-life paracetamol use (OR = 1.28, 95% CI = 1.21–1.36), with the former persisting at the school level, whereas the latter was no longer observed (OR = 1.35, 95% CI = 1.00–1.82 and OR = 0.94, 95% CI = 0.69–1.28, respectively). At ages 13–14 years, the strongest associations at the individual level were with current paracetamol use (OR = 1.57, 95% CI = 1.51–1.63) and open-fire cooking (OR = 1.46, 95% CI = 1.33–1.62); both were stronger at the school level (OR = 2.57, 95% CI = 1.84–3.59 and OR = 2.38, 95% CI = 1.52–3.73, respectively). Association with exposure to heavy traffic (OR = 1.31, 95% CI = 1.27–1.36) also persisted at the school level (OR = 1.40, 95% CI = 1.07–1.82). Most individual- and school-level effects were consistent, tending to exclude reverse causation. / Revisión por pares

Submitted by Angela Maria de Oliveira (amolivei@uepg.br) on 2017-11-21T16:37:05Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Luciana Dorochenko Martins.pdf: 5908866 bytes, checksum: e41aabef10040e1359e4e34497eb78ad (MD5) / Made available in DSpace on 2017-11-21T16:37:05Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Luciana Dorochenko Martins.pdf: 5908866 bytes, checksum: e41aabef10040e1359e4e34497eb78ad (MD5) Previous issue date: 2017-11-09 / O objetivo deste trabalho foi realizar uma revisão sistemática e um estudo clínico randomizado com o objetivo de avaliar a eficácia de um anti-inflamatório e analgésicos na redução da intensidade da dor pós-operatória em cirurgia de terceiros molares inclusos; e também elaborar um instrumento de medida que pudesse quantificar a auto percepção de pacientes sobre o desconforto em cirurgias dento-alveolares. Para isso foram realizados 3 estudos. O estudo 1, uma revisão sistemática; o estudo 2, um ensaio clínico e o estudo 3, a elaboração de um questionário para avaliar a auto percepção do paciente em relação ao procedimento cirúrgico odontológico. A revisão sistemática e meta-análise (estudo 1) teve o objetivo de avaliar se o cetorolaco reduz a intensidade da dor pós-operatória após a cirurgia dos terceiros molares inclusos em comparação com o uso de tramadol. Uma busca abrangente na literatura foi realizada, incluindo apenas ensaios clínicos randomizados que comparavam a intensidade da dor após a cirurgia de terceiros molares inclusos em pacientes adultos que usaram cetorolaco ou tramadol para analgesia. Nove estudos foram incluídos para análise qualitativa. Sete foram julgados como “indefinido” ou “alto” risco de viés e apenas 2 julgados como “baixo” risco de viés. Concluímos que existe falta de evidências para assegurar a superioridade do cetorolaco ou do tramadol na redução da dor pósoperatória após a extração dos terceiros molares inclusos. Um ensaio clínico randomizado, cruzado e triplo-cego (estudo 2) foi realizado com o objetivo de comparar a eficácia do cetorolaco (C) versus a sua combinação com tramadol (T)/paracetamol (P) administrado por via oral para controlar a intensidade da dor após a cirurgia de terceiros molares inferiores inclusos. Cinquenta e dois pacientes foram selecionados e submetidos a exodontias dos terceiros molares inferiores bilaterais. Duas intervenções cirúrgicas distintas foram realizadas, sempre pelo mesmo operador e separadas por um intervalo mínimo de 30 dias. Para uma exodontia, o indivíduo recebeu 1 comprimido de cetorolaco 10 mg mais uma cápsula de tramadol 37,5 mg/paracetamol 325 mg. Para a exodontia do lado oposto ao operado, o mesmo indivíduo recebeu 1 comprimido de cetorolaco 10 mg mais 1 cápsula de placebo. Esses tratamentos foram administrados 1 h antes da cirurgia e foram repetidos a cada 6 h durante 2 dias. A diferença na dor pós-operatória foi avaliada por quatro desfechos primários: intensidade da dor medida por uma escala visual analógica de 100 mm por 48 h (imediatamente, 3 h, 6 h, 9 h, 12 h, 24 h e 48 h após a cirurgia), medicação de resgate, avaliação global e efeitos adversos. Diferenças na intensidade da dor foram observadas nas diferentes avaliações do tempo (p < 0,05). A comparação de ambos os grupos em cada avaliação de tempo mostrou diferenças significativas apenas no período de 9 h, com menor intensidade de dor para o grupo C+T+ P (p = 0,005). A necessidade de analgésicos foi maior no grupo C, no entanto, a necessidade de antiemético foi maior no grupo de C+T+P. O número total de efeitos adversos foi maior no grupo de C + T + P. Os resultados mostraram que ambos os tratamentos farmacológicos empregados mostraram um bom controle da dor em cirurgias de terceiros molares inferiores inclusos. Embora o grupo da combinação tenha apresentado menor dor nas 9 h, a diferença foi pequena, não relevante clinicamente e causou mais efeitos adversos. O objetivo do estudo 3 foi criar um instrumento de medida que pudesse quantificar os desconfortos associados ao procedimento cirúrgico de pacientessubmetidos a cirurgias dento-alveolares (QCirDental). O instrumento QCirDental foi desenvolvido em duas etapas iniciais, (1) geração e seleção das perguntas ou itens e, (2) teste do instrumento com avaliação das propriedades de medida (consistência interna e responsividade). A amostra foi composta por 123 pacientes. Nenhum deles apresentou qualquer dificuldade em entender o QCirDental. O instrumento mostrou excelente consistência interna com coeficiente alfa de Cronbach de 0,83. A análise de componentes principais (Kaiser-Meyer-Olkin Measure of Sampling Adequacy 0,72 e Bartlett's Test of Sphericity com p < 0,001) mostrou seis dimensões do instrumento que explicam 67,5% da variância. Nesse estudo foi possível determinar que o instrumento ou questionário de auto percepção de cirurgia bucal dento-alveolar (QCirDental) possui excelente consistência interna, sendo um instrumento de fácil leitura e interpretação. / The aim of the present study was to perform a systematic review and a randomized clinical trial with the objective of evaluating the efficacy of an anti-inflammatory and analgesics in the reduction of the postoperative pain intensity after impacted third molar surgery; and also to elaborate a measurement instrument that could quantify the patients' self-perception about discomfort in dentoalveolar surgeries. Three studies were carried out. Study 1, a systematic review; study 2, a clinical trial and study 3, the elaboration of a questionnaire to evaluate the patient's self-perception regarding the dental surgical procedure. The systematic review and meta-analysis (study 1) aimed to evaluate if ketorolac reduces the intensity of postoperative pain after impacted third molars surgery compared to the use of tramadol. A comprehensive search in the literature was performed, including only randomized trials comparing pain intensity after impacted third molar surgery in adult patients who used either ketorolac or tramadol for analgesia. Nine studies were included for qualitative analysis. Seven were judged as “unclear” or “high” risk of bias and only two judged as “low” risk of bias. We conclude that there is a lack of evidence to assure the superiority of ketorolac or tramadol in the reduction of postoperative pain after extraction of the impacted third molars. A randomized, triple-blind, crossover clinical trial (study 2) was conducted to compare the efficacy of ketorolac (K) versus its combination with tramadol (T)/acetaminophen (A) administered orally to control pain intensity after mandibular third molars surgery. Fifty-two patients were selected and subjected to extractions of bilateral mandibular third molars. Two different surgical interventions were performed, always by the same operator and separated by a minimum interval of 30 days. For the extraction of one side, the patient received one tablet of ketorolac 10 mg plus one capsule of tramadol 37.5 mg/acetaminophen 325 mg. For the opposite side, the same individual received one tablet of ketorolac 10 mg plus one capsule of placebo. These treatments were administered 1 h prior to surgery and were repeated every 6 h for 2 days. The difference in postoperative pain was assessed by four primary end points: pain intensity measured by a 100 mm visual analogue scale for 48 h (immediately, 3 h, 6 h, 9 h, 12 h, 24 h and 48 h after surgery), rescue medication, overall assessment and adverse effects. Differences in pain intensity were observed among the different time assessments (p < 0.05). The comparison of both groups in each time assessment showed significant differences only in the period of 9 h, with lower level of pain intensity for group K+T+A (p = 0.005). The need of analgesics was higher in Group K however, the need of antiemetic were greater in Group K+T+A. The total number of adverse effects was higher in Group K+T+A. The results showed that both pharmacological treatments had a good control of pain in mandibular third molar surgery. Although the combination group showed lower pain at 9 h, the difference is small, not clinically relevant and this group showed much more adverse effects. The aim of study 3 was to develop and validate a questionnaire (QCirDental) to measure the burdens of oral surgery associated to dental extractions. The QCirDental was developed in two steps, (1) item generation and selection and (2) questionnaire pretest with evaluation of the instruments’ measurement properties (internal consistency and responsiveness). The sample was composed by 123 patients. None patient showed any difficulty to understand the QCirDental. The instrument showed excellent internal consistency with Cronbach's alpha coefficient of reliability of 0.83. The principal component analysis (Kaiser-Meyer-Olkin 10 Measure of Sampling Adequacy 0.72 and Bartlett's Test of Sphericity with p < 0.001) showed six dimensions explaining 67.5% of the variance. In this study, it was possible to determine that the questionnaire of dento-alveolar oral surgery (QCirDental) has excellent internal consistency, being an instrument of easy reading and interpretation.

The paper aims to mediate thin film chromatography analysis by means of drugs commonly found in households (analgesic-antipyretics) to secondary school and grammar students, or to college students. For this purpose, laboratory tasks have been designed to cover all levels of the Bloom pyramid so that the educational potential is as high as possible. This is closely related to the topic of drug expiration and treatment. Pupils and students should take on both the competences of knowledge, skills, and attitudes. Keywords: thin layer chromatography; TLC; chromatography in education; educational experiment; expiratory medication; drug handling; analgesic- antipyretics, acetylsalicylic acid, paracetamol