Dissertations / Theses: 'Drugs and infants'

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Proctor-Williams, Kerry, and Brenda Louw. "Infants and Children Prenatally Exposed to Drugs: Neonatal Abstinence Syndrome (NAS) and Neurodevelopmental Outcomes." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/1814.

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Moretti, Myla Emily. "Prospective follow-up of infants exposed to 5-aminosalicylic acid containing drugs through maternal milk." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0010/MQ40845.pdf.

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Veneranda, Ana Lucia Feitosa. "Use of potentially-nephrotoxic drugs in pediatic patients: prevalence, risk factores and prevention." Universidade Federal do CearÃ, 2006. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=334.

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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
Kidneys are vulnerable to chemical agent-induced injuries. Children (neonates and infants) are a particular at risk age group because they have renal functions less developed than that of adults. The exposure of children to medicines considered to be nephrotoxic agents - namely the aminoglycosides, nonsteroidal anti-inflammatory drugs (NSAID) and angiotensin converting enzyme (ACE) inhibitory drugs - should be avoided whenever possible. Hospitalized children are pointed out to be the group at greatest risk of nephrotoxicity due to their high level of exposure to these medicines as well as the frequent and improper use of non standardized medicines in this age range. To determine the prevalence of use of potentially-nephrotoxic drugs (PND) and the frequency of concomitant risk factors in hospitalized children younger than 2 years old in a medical ward in a pediatric hospital in Fortaleza, Brazil. A prospective, observational, follow-up study was developed. All children younger than 2 years old admitted to the general ward were included and followed-up. Sociodemographic data, pathological and pharmacotherapeutic antecedents were recorded, as well as information about the use of drugs and the attendance of risk factors for nephrotoxicity associated with aminoglycosides, NSAID and ACE inhibitors. Also, the occurrence of adverse events was identified. Data was taken from medical records and interviews with the mothers of the children. Statistical analysis involved cumulative frequency, cumulative percentage, central tendency measures, Student âtâ test and ANOVA. During the study period (September/2005 to March/2006), 120 admissions were recorded. Three patients were excluded because of incomplete data. The results represented 117 admissions that affected 103 different children. The prevalence of the use of PND was 96,6%. A total of 1065 drugs were used, 69% with potential intrinsic nephrotoxicity based on available literature. The mean number of PND used was 6,3 Â 4,0 per patient. The PND most frequently used were: metamizole (10,1%), ranitidine (6,2%) and prednisone (5,1%). Around 18% of children used aminoglycosides, 65,8% and 4,3% had taken NSAID and ACE inhibitory drugs respectively. A total of 368 risk factors for nephrotoxicity were detected (3,5Â1,8 risk factors/patient). The most frequent factors were: the use of at least one PND (30,7%), the use of 2 or more PND (28,3%) and the use of NSAID concomitantly with that of potassium-rich salt substitutes(10%).The PND use was considered high when compared with published data from this studied age group. The frequency of risk factors for nephrotoxicity also reached considerable levels. It would be important to know if there exist safer therapeutic alternatives and what preventative measures could be adopted in each case. The contribution of a clinical pharmacist to a safe pharmacotherapy for hospitalized children would be a strategy for reducing PND-associated risk.
Os rins sÃo bastante vulnerÃveis a danos produzidos por agentes quÃmicos. Dentre as substÃncias nefrotÃxicas estÃo os medicamentos, os quais merecem destaque devido Ã ampla exposiÃÃo aos mesmos. Alguns grupos, como aminoglicosÃdeos, antiinflamatÃrios nÃo-esteroidais (AINE) e inibidores da enzima conversora de angiotensina (IECA) sÃo muito conhecidos pelo seu potencial nefrotÃxico intrÃnseco. As crianÃas menores (neonatos e lactentes) sÃo dignas de atenÃÃo especial no que se refere a essa questÃo, porque freqÃentemente usam medicamentos e, alÃm disso, a capacidade funcional de seus rins Ã menor do que a dos adultos. A melhor maneira de tratar a questÃo da nefrotoxicidade Ã prevenindo-a. Determinar a prevalÃncia de uso de medicamentos potencialmente nefrotÃxicos (MPN) e observar a presenÃa de condiÃÃes que favorecem ao desenvolvimento da nefrotoxicidade (fatores de risco) em crianÃas menores de dois anos de idade internadas em enfermaria geral de um hospital pediÃtrico em Fortaleza â Brasil. Estudo observacional, prospectivo, de seguimento de pacientes. Todas as crianÃas menores de dois anos admitidas na enfermaria âEâ foram incluÃdas e monitorizadas. InformaÃÃes sociodemogrÃficas, antecedentes patolÃgicos e farmacolÃgicos foram registrados, bem como informaÃÃes sobre o uso de medicamentos, presenÃa de fatores de risco para nefrotoxicidade associada a aminoglicosÃdeo, AINE e IECA, e ocorrÃncia de eventos adversos. Os dados foram coletados dos prontuÃrios mÃdicos e atravÃs de entrevista com os responsÃveis pelas crianÃas, sendo analisados estatisticamente usando medidas de freqÃÃncia, tendÃncia central e os testes âtâ de Students e Anova. Durante o perÃodo de estudo (setembro/2005 a marÃo/2006), ocorreu um total de 120 admissÃes na enfermaria; trÃs dos pacientes foram excluÃdos do estudo porque tinham dados incompletos. Os resultados se referem a 117 admissÃes correspondentes a 103 crianÃas. A prevalÃncia de uso de MPN foi de 96,6%. Do total de 1065 itens de prescriÃÃo consumidos, 68,6% tinham potencial nefrotÃxico intrÃnseco. O nÃmero mÃdio de MPN utilizados foi 6,3 Â 4,0 por paciente. Dentre os MPN mais usados estavam: dipirona (10,1%), ranitidina (6,2%) e prednisona (5,1%). Dois por cento das crianÃas usaram aminoglicosÃdeos, 7,3% usaram AINE e 0,8% utilizaram IECA. Foram detectados 368 fatores de risco para nefrotoxicidade, com uma mÃdia de 3,15 Â 1,8 fatores de risco/paciente. Os fatores de risco mais freqÃentes foram: uso de, no mÃnimo, um MPN (30,7% do total de fatores); uso de 2 ou mais MPN concomitantemente (28,3%) e o uso de AINE concomitante ao uso de suplementos de potÃssio (10%). O uso de MPN na faixa etÃria estudada foi considerado elevado. A freqÃÃncia de fatores de risco para nefrotoxicidade tambÃm ocorreu em nÃveis preocupantes. Seria importante conhecer se existiam alternativas mais seguras em cada caso e que medidas preventivas poderiam ser adotadas. A inclusÃo do farmacÃutico clÃnico na atenÃÃo a crianÃas hospitalizadas seria uma estratÃgia com grande potencial de impacto na reduÃÃo de riscos associados aos MPN.

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Horstman, Emily, Kelsi Sanders, Makaela Nava-Sifuentes, Spencer Townsend, Caroline H. Bowman, Kerry Proctor-Williams, and Niki Carder. "Infants with Neonatal Abstinence Syndrome: Who Receives SLP Services in the NICU?" Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/195.

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Introduction Neonatal abstinence syndrome (NAS) is a health condition in infants that results from the sudden discontinuation of substances that infants were exposed to in utero (Kocherlakota, 2014). Typical symptoms include: hyperirritability, sweating, hypertension, tremors, sleep deprivation, and seizures (Kocherlakota, 2014). The role of a SLP in treating infants with NAS in the NICU includes evaluation, assessment, and treatment of the feeding cycle. Our research is an early exploratory and descriptive study of the pre-natal, peri-natal, and post-natal characteristics of infants with NAS who required SLP assessment and intervention as opposed to those who did not. Our aim was to examine possible predictors of infants with feeding and swallowing difficulties. Methods Data was collected from a local hospital system that conducted a five-year retrospective chart review study. From charts of 140 infants in the NICU, infants were placed into two groups: infants who received SLP services (SLP group) and infants who did not receive SLP services (NSLP group). From those charts, 26 infants with NAS who received SLP services were placed in SLP group based on the availability of a match in NSLP group. Infants in both groups were matched based on gestational age, year of birth, and gender. Results/Conclusion There were no significant differences found between SLP group and NSLP groups in: number of prenatal visits, week/timing of initial prenatal visit, and dosage of buprenorphine taken by the mother. The two groups did not differ (all ps>.18) in their types of drug use, average dosage of buprenorphine taken, average number of prenatal visits, or average week of first visit. There was a statistically significant difference in maternal age in the SLP group (p<.05; M=29.7 years, SD=5.4) and in NSLP group (M=26.7 years, SD=4.3.). There was no statistically significant difference in initial measurements of weight, head circumference, length, Apgar scores at birth, and number of complications between groups. There were no significant differences found in NAS scores between groups regarding the highest NAS score or average NAS score, number of NAS scores and first day of collection or number of days collected. There was a statistically significant difference in the number of prescription drugs administered. Infants in SLP group had more prescription drugs on average (M=1.50, SD=.89) than NSLP group (M=1.04, SD=.20). There was a statistically significant difference in the amount of weight gained (SLP group gained 229 more grams) and in infant length of stay and overall cost (SLP group on average stayed in the NICU one week longer and cost $22,896 more). Little research has been conducted regarding NAS and the impact it has on feeding and swallowing. We found that there are statistically significant differences among infants who were in SLP and NSLP groups. It cannot be determined how many full-term infants have dysphagia; however, from a clinical opinion it is thought that most full-term babies with dysphagia also have a neurological impairment.

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Moser, Michele R. "Understanding and Addressing the NAS and Drug Exposed Infant Problem in NE TN." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/5000.

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Damji, Khadija Katy. "Sucking function in infants : the effects of maternal drug abuse." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/27867.

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Infants of mothers who have received narcotics on a continuous basis during pregnancy are born physically dependent. Drug withdrawal, one of many detrimental effects, is initially the most apparent. Neonatal abstinence syndrome (NAS) was originally described as a generalized disorder characterized by signs of central nervous system hyperirritability, gastrointestinal dysfunction, respiratory distress, and a host of vague autonomic manifestations. Recent studies have suggested that these same signs follow withdrawal from other addicting drugs as well. Feeding problems are the most common and important concomitants of neonatal withdrawal, because sucking function is uncoordinated, ineffectual and poorly sustained. Previous studies have shown a natural history of recovery of sucking dysfunction during recovery from NAS. A disposable and practical apparatus for monitoring nutritive sucking behaviour was developed, based on a prototype previously described in the literature. A weighted scoring system which encompasses the full spectrum of withdrawal signs was also designed. No significant difference in sucking rate was observed between normal and NAS babies on day 1 (p=0.8). There was a highly significant difference on day 2 (prO.0001), day 3 (p=0.0005), and day 4 (p=0.006). No significant difference in nutrient consumption was observed between normal and NAS babies on day 1 (p=0.9) and day 2 (p=0.8). A significant difference was observed on day 3 (p=0.006) and day 4 (p=0.03). A significant inverse correlation was demonstrated between both sucking rate and nutrient consumption with the classical clinical signs of withdrawal over the first two months of life (r=-0.57, -0.51, respectively). The periodic monitoring of sucking rate of the passively addicted infant provides an objective gauge of the seventy of withdrawal in NAS, eliminating the subjectivity of evaluating changes in clinical signs. Therefore, it is recommended that sucking rate measurements be instituted as a standard guide to the management of withdrawal in these infants.
Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate

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O'Callaghan, Christopher. "Aerosolised drug therapy in infancy." Thesis, University of Nottingham, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305089.

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Gerrard, Stephen Edmund. "A novel infant therapeutic delivery system for drugs, nutrients and anti-viral agents." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648462.

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Kusmorini, N. "The effects of psychoactive drugs on aspects of mother-infant behaviour in laboratory mice." Thesis, Swansea University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.637833.

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The possibility that isolation or 'distress' calling in newborn rodents can be used to screen for anxiolytic activity was explored. The effects of a wide range of drugs that influence the benzodiazepine / GABA receptor complex, serotonergic, noradrenergic, dopaminergic and cholinergic transmitter systems on ultrasonic calling were systematically assessed, in 5-6 day old mouse pups, under controlled temperature conditions. Benzodiazepine agonists reliably decreased ultrasonic calling whereas inverse agonists increased it. The benzodiazepine antagonists, which had no significant influences per se on this measure, blocked the effects of both direct and inverse benzodiazepine agonists on ultrasonic calling. GABA agonists reduced ultrasonic calling although GABA antagonists had no significant effects on this measure. These antagonists did, however, block the effects of the agonist muscimol. Exposure of mouse pups to PTZ increased the number of calls. The action of PTZ was blocked by the benzodiazepine antagonist, Ro 15-1788. Three out of four serotonin agonists tested in these studies increased the number of ultrasonic calls, while the antagonists of serotonin suppressed such production. These effects on ultrasonic calls appear mediated by the 5-HT receptor, as the actions of some agonists are reliably blocked by specific antagonists. Tests with noradrenaline antagonists (sensu Carlson, 1986) (except AMPT) decreased ultrasonic calling. Apomorphine and sulpiride respectively increased and decreased the number of ultrasonic calls. With drugs acting via all receptors, changes in core body temperature and performance on the inclined plane test were routinely observed to identify possible indirect actions. Increases and decreases in calling generally appeared independent of thermoregulatory or sedative actions of drugs. It was concluded that ultrasonic calling can be used to quickly and accurately assess some classes of drugs for their anxiolytic or anxiogenic properties. Other experiments examined nest building and the behaviour of reproductive female mice after treatment with chlorpromazine, d-amphetamine or morphine sulphate. These preliminary data suggested that sedative drugs have major impacts on nest building and other activities, but additional studies have to be conducted to determine whether other tests based on the mother-infant bond will prove to be of utility in the study of psychoactive drugs.

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Bader, Mohammad Y., Alex Lopilato, Leslie Thompson, and RanjitI Kylat. "Aminophylline-associated hyponatremia in a premature infant." Published by Wolters Kluwer - MedKnow, 2017. http://hdl.handle.net/10150/625943.

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Hyponatremia is common in preterm infants. The causes are usually related to the inability of the premature kidneys to excrete a given water load, excessive sodium losses, or inadequate sodium intake. Here, we present a case of severe hyponatremia in an extreme preterm infant, associated with the use of aminophylline. Aminophylline was administered intravenously on day 1 for the treatment of apnea of prematurity. On day 3, the patient developed hyponatremia which was not responsive to sodium replacement and fluid restriction. Due to concerns of aminophylline‑induced hyponatremia, aminophylline was discontinued on day 6, and within 48 h of discontinuation, serum sodium normalized without the need for sodium supplementation. The purpose of the case report is to present a rare complication associated with aminophylline use and to shed light on potential deleterious effects associated with drug shortages.

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Ochoa, Theresa J., Joaquím Ruiz, Margarita Molina, Valle Luis J. Del, Martha Vargas, Ana I. Gil, Lucie Ecker, et al. "High frequency of antimicrobial drug resistance of diarrheagenic Escherichia coli in infants in Peru." American Society of Tropical Medicine and Hygiene, 2014. http://hdl.handle.net/10757/314286.

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Abstract. In a prospective passive diarrhea surveillance cohort study of 1,034 infants of low socioeconomic communities in Lima, Peru, we determined the prevalence and antimicrobial drug susceptibility of the diarrheagenic Escherichia coli . The prevalence of diarrheagenic E. coli was 29% (161 of 557) in children with gastroenteritis and 30% (58 of 195) in the control group without diarrhea. The most common E. coli pathogens in diarrhea were enteroaggregative E. coli (EAEC) (14%), enteropathogenic E. coli (EPEC) (7%), diffusely adherent E. coli (DAEC) (4%), and enterotoxigenic E. coli (ETEC) (4%). Diarrheagenic E. coli as a group exhibited high levels of antimicrobial drug resistance in diarrheal cases to ampicillin (85%), cotrimoxazole (79%), tetracycline (65%), and nalidixic acid (28%). Among individual E. coli groups in patients with diarrhea, DAEC and EAEC exhibited significant higher frequencies of resistance to ampicillin, cotrimoxazole, tetracycline and nalidixic acid than EPEC and ETEC. Antimicrobial drug resistance to ampicillin and cotrimoxazole were more frequent in E. coli isolated from diarrheal samples than controls, which reflected greater antibiotic exposure in patients with gastroenteritis.

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Bango-Sanchez, Vivian M. "The Effects of Peer Teaching of Infant Massage on General Self-Efficacy and Mother Infant Attachment Among Mothers in a Residential Rehabilitation Facility for Drug Addiction and Substance Abuse." FIU Digital Commons, 2010. http://digitalcommons.fiu.edu/etd/168.

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Approximately 200 million people, 5% aged 15-64 worldwide are illicit drug or substance abusers (World Drug Report, 2006). Between 2002 and 2005, an average of 8.2% of 12 year olds and older in the Miami, Fort Lauderdale metropolitan areas used illicit drugs (SAMHSA, 2007). Eight percent of pregnant women, aged 15 to 25, were more likely to have used illicit drugs during pregnancy than pregnant women aged 26 to 44. Alcohol use was 9.8% and cigarette use was 18% for pregnant women aged 15 to 44 (SAMHSA, 2005). Approximately a quarter of annual birth defects are attributed to the exposure of drugs or substance abuse in utero (General Accounting Office, 1991). Physical, psychological and emotional challenges may be present for the illicit drug/substance abuse (ID/SA) mother and infant placing them at a disadvantage early in their relationship (Shonkoff & Marshall, 1990). Mothers with low self efficacy have insecurely attached infants (Donovan, Leavitt, & Walsh, 1987). As the ID/SA mother struggles with wanting to be a good parent, education is needed to help her care for her infant. In this experimental study residential rehabilitating ID/SA mothers peer taught infant massage. Massage builds bonding/attachment between mother and infant (Reese & Storm, 2008) and peer teaching is effective because participants have faced similar challenges and speak the same language (Boud, Cohen, & Sampson 2001). Quantitative data were collected using the General Self-Efficacy and Maternal Attachment Inventory-Revised Scale before and after the 4-week intervention program. A reported result of this study was that empowering ID/SA mothers increased their self-efficacy, which in turn allowed the mothers to tackle challenges encountered and created feelings of being a fit mother to their infants. This research contributes to the existing database promoting evidence-based practice in drug rehabilitation centers. Healthcare personnel, such as nurse educators and maternal-child health practitioners, can develop programs in drug rehabilitation centers that cultivate an environment where the ID/SA rehabilitating mothers can peer teach each other, while creating a support system. Using infant massage as a therapeutic tool can develop a healthy infant and nurture a more positive relationship between mother and infant.

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Best, Emma Women's &amp Children's Health Faculty of Medicine UNSW. "Once daily gentamicin in infants and children: an evaluation of safety and the role of therapeutic drug monitoring in minimising toxicity." Awarded by:University of New South Wales, 2007. http://handle.unsw.edu.au/1959.4/35192.

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AIMS: To assess (i) the safety of once daily dosing (ODD) of gentamicin by systematic evaluation of ototoxicity and nephrotoxicity; and (ii) the usefulness of therapeutic drug monitoring (TDM) in a paediatric cohort. METHOD: Infants and children with suspected or proven gram negative sepsis were enrolled prospectively to receive ODD gentamicin at 7 mg/kg/day. Neonates were excluded. Hearing and renal function were assessed at baseline, during and after therapy by otoacoustic emissions (OAE) and by either serum creatinine or glomerular filtration rate. Abnormal OAE were followed with audiometry. TDM was performed using an interval adjusted graphical method (Hartford nomogram) with levels taken between 6-14 hours after dose. Assessment of efficacy (clinical and microbiological) was a secondary outcome measure. RESULTS: There were 106 episodes of therapy in 79 children (median age 5.6 years; range 1 month - 16 years), 60% of which were for febrile neutropaenia. Evaluation was complete in 88% (93/106) for ototoxicity and 92% (98/106) for nephrotoxicity. Two children (1.88%, 95% CI 0.10 - 7.13) experienced permanent hearing loss. Three children did not complete full assessment after preliminary abnormalities on OAE. Incorporating these cases gives a ???worst case scenario??? incidence of 4.71% (95% CI 1.71 - 10.91) possible ototoxicity. One child (0.94%, 95% CI < 0.10 - 5.73) experienced transient nephrotoxicity. No ???toxic??? serum gentamicin levels were detected, including in those children who experienced clinical toxicity. All children with detectable toxicity were undergoing treatment for malignancies and had received nephro or ototoxic medications prior to the gentamicin course. Complete or partial efficacy was seen in 93% (non oncology) and 78% (oncology) treatment episodes, equivalent to prior literature reports. CONCLUSION: In this systematically evaluated paediatric cohort receiving ODD gentamicin, toxicity occurred infrequently and only in those with identifiable risk factors. TDM did not identify children who developed clinical toxicity. The development of toxicity appears to be associated with factors such as underlying medical condition, prior courses of gentamicin, exposure to other oto or nephrotoxic medications, all of which may be more predictive of toxicity than elevated serum gentamicin levels. TDM in healthy children on short course gentamicin appears unnecessary, but may be warranted in conjunction with renal and hearing assessments in those with risk factors.

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Boc, Susan. "Aerosolized Surfactants: Formulation Development and Evaluation of Aerosol Drug Delivery to the Lungs of Infants." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5577.

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The overall aim of this research project was to develop surfactant dry powder formulations and devices for efficient delivery of aerosol formulations to infants using the excipient enhanced growth (EEG) approach. Use of novel formulations and inline delivery devices would allow for more efficient treatment of infants suffering from neonatal respiratory distress syndrome and bronchiolitis. A dry powder aerosol formulation has been developed using the commercial product, Survanta ® (beractant) and EEG technology to produce micrometer-sized hygroscopic particles. Spray drying and formulation parameters were initially determined with dipalmitoylphosphatidylcholine (DPPC, the dominant phospholipid in pulmonary surfactant), which produced primary particles 1 um in size with a mass median aerodynamic diameter of 1-2 um. Investigation of dry powder dispersion enhancers and alcohol concentration on the effect of powder aerosol characteristics were performed with the Survanta-EEG formulation. The optimal formulation consisted of Survanta ® , mannitol and sodium chloride as hygroscopic excipients, and leucine as the dry powder dispersion enhancer, prepared in 20% v/v ethanol/water. The powders produced primary particles of 1 um with >50% of the particles less than 1 um. The presence of surfactant proteins and surface activity were demonstrated with the Survanta-EEG formulation following processing. A novel containment unit dry powder inhaler (DPI) was designed for delivery of the surfactant-EEG formulation using a low volume of dispersion air. Studies explored optimization of air entrainment pathway, inlet hole pattern, delivery tube internal diameter and length. With 3- 10 mg fill masses of spray dried surfactant powder, the DPI enabled delivery of >2 mg using one 3-mL actuation of dispersion air. Overall, it was possible to deliver >85% of the loaded fill mass using three actuations. Nebulized aerosol formulations are characterized with low delivered doses. Using a novel mixer-heater delivery system, the highest estimated percent lung dose achieved during realistic in vitro testing of a Survanta-EEG formulation aerosolized with a commercial mesh nebulizer was when nebulization was synchronized with inhalation of the breathing profile. Design changes to the mixer-heater system eliminated the need for synchronization, achieving an estimated percent lung dose of 31% of the nominal, an improvement compared with existing systems that achieve approximately <2% lung dose.

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McGlone, Laura. "Flash visual evoked potentials and early visual development in infants born to drug misusing mothers." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3184/.

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Background / Aims: Maternal drug misuse in pregnancy is a significant clinical and public health problem. Consequences for the newborn infant include prematurity, intrauterine growth restriction (IUGR) and neonatal abstinence syndrome (NAS). There is increasing evidence that maternal drug misuse in pregnancy may have longer term adverse effects on infant visual and neurodevelopmental outcome. Most of the evidence regarding visual outcomes in particular derives from small uncontrolled studies with a lack of adequately powered, controlled studies to date. The visual evoked potential (VEP) can be used to assess the integrity and maturity of the infant visual pathway and both visual and neurodevelopmental abnormalities can be predicted by abnormal VEPs in infancy. Drug misuse is also associated with alteration of the VEP in adults and in animal models. Many drugs used in pregnancy can cross the placenta and enter the fetal circulation, including illicit drugs and prescribed methadone, which is the currently recommended treatment for pregnant opiate-dependent women. Hitherto few studies have investigated the effects of maternal drug misuse upon the newborn infant VEP. This study investigates in detail the effects of prescribed methadone and additional illicit drug use in pregnancy upon the infant VEP recorded at birth and at six months of age, and explores any association with NAS. The range and incidence of visual and neurodevelopmental abnormalities at six months of age is described, and how these relate to a history of NAS and the pattern of in utero drug exposure is explored. Pilot work: Pilot work demonstrated the feasibility of recording neonatal flash VEPs in a small group of infants exposed to methadone in utero, and showed that drug exposed infants had abnormal VEPs compared to unmatched controls. A further pilot study described longer term visual outcomes, which included nystagmus, reduced visual acuity and strabismus, in a selected group of infants and children exposed to methadone in utero, thus informing clinical and electrophysiological assessment at six months of age. The pilot studies were followed by a major prospective cohort study. Prospective Study: One hundred and two term infants of mothers prescribed substitute methadone during pregnancy and 50 comparison infants matched for birth weight, gestation and socio-economic group were recruited in the neonatal period. Flash and flicker VEPs were recorded from the occipital scalp of infants within three days of birth. Drug exposure was determined by maternal history, maternal and infant urine and meconium toxicology. Excess alcohol exposure in utero was determined by elevated fatty acid ethyl esters in meconium. Neonatal flash VEPs were classified as mature, typical, or immature according to waveform morphology, and amplitude and latencies measured. Flicker VEPs were analysed using a fast-Fourier transformation and responses at each flicker frequency determined. The same cohort of drug-exposed and comparison infants was invited for clinical visual evaluation at six months of age in conjunction with pattern-onset VEPs and Griffiths developmental assessment. Results: Neonatal testing: Neonatal VEPs were successfully recorded from 100 drug-exposed infants and 50 matched comparison infants at a median age of 24 hours (IQR 13-44). Gestational age, birth weight and socio-economic group did not differ between groups. Flash VEPs from methadone-exposed infants had fewer P1 components (p=0.001), and were more likely to be of immature waveform (p<0.001) compared to comparisons. VEPs from methadone-exposed infants were also smaller in overall amplitude (median 27µV vs 39.5µV, p<0.001). The relative risk of an abnormal VEP in the methadone-exposed cohort was 5.6 with an attributable risk percent of 82%. The majority of infants were exposed to illicit drugs in addition to prescribed methadone, most commonly opiates (74%) and benzodiazepines (66%). VEPs did not differ between infants exposed to opiates only, those additionally exposed to benzodiazepines and those exposed to stimulants. Regression analysis confirmed that the difference in VEP parameters between drug-exposed and comparison infants was associated with methadone exposure and not other drugs of misuse. 48% of the methadone-exposed cohort developed NAS requiring pharmacological treatment; there was no association between neonatal VEPs and subsequent onset or severity of NAS. Flicker VEP analysis demonstrated an optimal flicker frequency of 4.6 Hz in both groups, but there were few differences in the proportion of responses between groups. Six month follow-up: Retention rate to six month follow-up was 79% for the methadone-exposed cohort and 52% for comparison infants. Age at assessment (median 27 weeks, range 26-30 wk), weight and OFC did not differ between groups. The demographic characteristics of comparison infants who were followed up were compared to those of comparison infants who were not followed up. There were no significant differences in birth weight (2 sample t-test p=0.445), OFC (2 sample t-test p=0.712), gestation (Mann-Whitney test p=0.984), 5-minute Apgar score (Mann-Whitney test p=0.263) or DEPCAT score (Mann-Whitney test p=0.258) between groups. Methadone-exposed infants were more likely to have visual abnormalities than comparison infants, even after correcting for excess in utero alcohol exposure (40% vs 8%; adjusted p=0.007). Abnormalities in the methadone-exposed cohort included nystagmus (11%), strabismus (25%) and reduced visual acuity (22%). The relative risk of an abnormal visual outcome in the methadone-exposed cohort was 5.1 with an attributable risk percent of 80%. Electrophysiological abnormalities persisted at six months of age: methadone- exposed infants had smaller amplitude pattern VEPs (25 μV vs 34 μV; p=0.005) with delayed peak latencies (115ms vs 99ms; p=0.019) and fewer responses at the small check size (p=0.003), compared to controls. Methadone-exposed infants had significantly lower neurodevelopmental scores compared to comparison infants (GQ 97 for cases vs 105 for controls; p<0.001), even after correcting for maternal smoking, antidepressant treatment and excess alcohol consumption during pregnancy. Infants exposed to poly-drug misuse and treated for NAS in the newborn period performed particularly poorly on their neurodevelopmental scores. Visual impairment was an independent predictor of poor neurodevelopmental outcome and most infants scoring <85 on neurodevelopmental assessment had co-existing visual problems. Conclusions: In utero exposure to prescribed methadone and other substances of misuse is associated with an alteration in visual electrophysiology in the newborn period suggestive of immature visual maturation. These changes are independent of additional benzodiazepine or stimulant exposure, and appear to be associated with prescribed substitute methadone. At six months of age, there is a high incidence of clinical visual abnormalities in infants exposed to methadone and other drugs of misuse in utero. Persistence of electrophysiological abnormalities beyond the neonatal period suggests that opiates may have a longer term effect on the developing visual system. Drug-exposed infants also have poorer neurodevelopmental scores than matched comparison infants after correcting for maternal smoking and excess alcohol intake. The bias of loss to follow-up was minimised by the high retention rate of drug-exposed infants. Although there was a higher loss of comparison infants, there were no differences in demographic characteristics between comparison infants followed up and those not followed up, suggesting the groups were similar. In addition, published data suggest the incidence of visual abnormalities described in the comparison population to be representative of the larger population.

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Moser, Michele R. "Neonatal Abstinence Syndrome (NAS): Infant Victims of Tennessee’s Prescription Drug Abuse Epidemic." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/5001.

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17

Aluru, Srikanth. "Molecular characterization of Leishmania infantum strains and evaluation of new drugs to cure visceral leishmaniasis." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5083.

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La leishmaniose viscérale (LV) est la forme la plus sévère de la leishmaniose humaine. Elle est transmise par la piqûre d'un phlébme. La leishmaniose viscérale est mortelle en l'absence de traitement. Les options thérapeutiques courantes contre la leishmaniose viscérale sont limitées. En région méditerranéenne, la LV est due à Leishmania infantum, zoonose dont le chien est le principal réservoir. A côté de quelques cas d'infection systémique, un nombre important d'humains porteurs asymptomatiques a été mis en evidence. En première partie, nous avons étudié l'intérêt du MultiLocus Microsatellite Genotyping (MLMT) pour l'identification des souches de Leishmania du sud de la France. Par MLMT nous avons étudié la variabilité génétique de différentes souches et recherché une association avec les différentes formes cliniques, la résistance aux médicaments et les phénomènes de rechutes. Nous avons observé une hétérogénéité génétique entre les différentes souches de L. infantum MON-1. Si l'association de certains génotypes avec les différentes expressions cliniques de la leishmaniose n'a pu être démontrée, nous avons par contre observé une répartition préférentielle géographique de certains génotypes. En deuxième partie, nous avons mis au point un protocole expérimental destiné au criblage de nouveaux agents anti-Leishmania infantum ayant pour cible la machinerie cellulaire mise en route par la cellule hôte pour l'élimination du parasite intracellulaire. Nos résultats ont montré que les altérations du système de trafic intracellulaire de la cellule-hôte induites par certains composés étaient corrélées à la mort du parasite et à son élimination
Visceral leishmaniasis (VL) is the most severe form of Human Leishmaniases, which occurs when protozoan parasites Leishmania donovani or L. infantum, given by phlebotomine sandfly bites. The disease is fatal when untreated. Current treatment options against VL are very limited with few drug molecules, often expensive, not always safe and able to induce resistance phenomenon.In this report, we have characterized on one hand, different genetic variants of Leishmania infantum strains isolated in different geographical areas from southern France and on the other hand have identified new potential anti-Leishmania infantum compounds and characterized their molecular mechanism of action.In the first part, we studied the interest of Multilocus Microsatellite Genotyping (MLMT) for the identification of Leishmania strains from southern France. By genotyping technique MLMT, we studied the genetic variability of different strains and sought an association with different clinical forms of leishmaniasis, resistance to drugs and relapse. We observed genetic heterogeneity among different strains of L. infantum-MON-1. we observed a preferential geographic distribution of certain genotypes.In the second part, we have developed an experimental protocol for the screening of new anti-Leishmania infantum compounds that target the host cell machinery responsible for the intracellular parasite killing, we studied the different steps of endocytic pathways potentially targeted by these compounds. Our results showed that with some compounds, modifications of the intracellular trafficking of the host cell were correlated with parasite death and its elimination

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Bailey, Beth A., Judy G. McCook, Andrea D. Clements, and Lana McGrady. "Infant Birth Outcomes Among Substance Abusing Women: Why Quitting Smoking Is Just as Important as Quitting Harder Drugs." Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etsu-works/7272.

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19

Cairns, Matthew. "Intermittent preventive treatment for malaria in infants and children protective mechanism drug choice and optimal dosing strategies." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.536869.

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20

Sousa, André Filipe Simões de Carvalho de. "Investigation of trypanothione synthetase of Leishmania infantum as a potential target for new anti-parasitic drugs." Master's thesis, Faculdade de Ciências e Tecnologia, 2011. http://hdl.handle.net/10362/6344.

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Dissertação para obtenção do Grau de Mestre em Biotecnologia
Leishmania infantum is a protozoan parasite of the Trypanosomatidae family, responsible for human and canine leishmaniasis in Mediterranean countries. Control of these vector-borne diseases is unsatisfactory and new chemotherapeutics are urgently needed. Trypanothione biosynthesis, owing to its unique and essential character, is regarded as an attractive target for therapeutic intervention. Trypanothione is a bis-(glutathionyl)spermidine conjugate, responsible for redox homeostasis in trypanosomatids. It is synthesized by the sequential addition of two molecules of glutathione to a spermidine molecule. Trypanothione synthetase (TRYS), which catalyzes both conjugation steps, has no counterpart in mammals and is essential to Trypanosoma brucei. This scenario is somewhat different in L. infantum, which harbors one additional enzyme mono(glutathionyl)spermidine synthetase or GSPS capable of driving the first step of trypanothione biosynthesis. Since mono(glutathionyl)spermidine can replace some metabolic functions of trypanothione in vitro, the actual significance of TRYS is still disputed in GSPS-harboring trypanosomatids. This work aimed at clarifying this issue by functionally characterizing both TRYS and GSPS in L. infantum promastigotes (insect stage) and amastigotes (mammalian stage), employing a classical gene replacement strategy. Concerning TRYS, elimination of both alleles in promastigotes was only possible upon complementation with an extrachromosomal copy of the gene. Maintenance of this episome for 6 months in the absence of drug pressure proved that TRYS is crucial and cannot be replaced by GSPS. Work is on going to assess TRYS essentiality in amastigotes. In parallel, we have initiated the chemical validation of TRYS using a N5-substituted paullone (FS-554) that irreversibly inhibits the enzyme in vitro. We observed that the leishmanicidal effect of FS-554 towards promastigotes and intramacrophagic amastigotes correlated with TRYS expression levels, confirming that this enzyme can be targeted by drug-like compounds in the cell context. In what regards GSPS, production of homozygous knockouts is still underway to be used in future work.
Supported by a grant (PTDC/BIA-MIC/10091/2008) from “Fundação para a Ciência e Tecnologia”(FCT)

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Murtland, Patricia A. "Effect of prepregnancy weight, prenatal weight gain and smoking on infant birth weight." Virtual Press, 1995. http://liblink.bsu.edu/uhtbin/catkey/941359.

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The purpose of this study was to determine the relationship- between prenatal weight gain relative to initial weight and change in smoking habits relative to prepregnancy smoking habits on infant birth weight. The convenience sample was 100 women who had been prenatal clients at a clinic for low income women and who delivered term infants during a one year period. Women were selected who had term deliveries and were without medical problems during the pregnancy.Prepregnancy weight-for-height was determined using the 1959 Metropolitan Life Insurance Table. Weight gain throughout the pregnancy was charted on the appropriate graph. Changes in smoking habits during the pregnancy were evaluated verbally. Roy's Adaptation Model was the conceptual framework for this study. The physiological mode of this model depicts people as individuals who are constantly adapting to a changing environment. Procedures for the protection of human subjects were followed.The first research question illustrated that women who gained adequate weight and reduced or quit smoking had infants with higher birth weights. The second research question showed that, overall, women who quit or reduced the amount smoked early in pregnancy had infants with higher birth weights than women who quit or reduced later in pregnancy or-who did not change smoking habits. The third research question determined that nonsmokers had infants with higher birth weights than smokers.Women who smoke will have infants with lower birth weights than those that do not smoke. Women with inadequate weight gains during pregnancy are more likely to have infants: with lower birth weights than women with adequate weight gains. Health care providers must be able to relay, the risks of inadequate weight gain and smoking to pregnant women.
School of Nursing

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22

Smit, Odette. "Early infant HIV diagnosis and characterization of HIV drug resistance in Gauteng, South Africa." Diss., University of Pretoria, 2021. http://hdl.handle.net/2263/79141.

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Despite the high prevalence of the human immunodeficiency virus (HIV) in South African women of reproductive age, the South African (SA) Prevention of Mother-to-Child Transmission (PMTCT) programme has significantly reduced the incidence of new HIV infections in infants from >20% in 2004 to <2% and overall MTCT approximately >5%. The PMTCT programme, however, faces challenges in terms of early infant diagnosis (EID) because of HIV polymerase chain reaction (PCR) indeterminate results as well as HIV drug resistance (HIVDR) secondary to antiretroviral therapy (ART) exposure of mothers and infants. The National Health and Laboratory Services (NHLS) uses the Roche COBAS®AmpliPrep (CAP)/COBAS®TaqMan® (CTM) HIV-1 Qualitative Test (Roche Molecular Systems, Pleasanton, CA) (CAP/CTM) platform as part of EID. Recently, the Roche cobas® 6800/8800 System has been introduced to test HIV viral load and HIV DNA PCR for EID. The platform is already processing samples for HIV viral load; however, verification for HIV DNA PCR for EID with dried blood samples (DBS) is needed, especially for CAP/CTM HIV PCR indeterminate results (Cycle threshold [Ct]>33 with any relative fluorescent intensity [RFI] value or Ct≤33 and RFI <5 on the CAP/CTM, Ct>38 on the Roche cobas® 6800/8800 System). In addition, HIVDR in newly diagnosed infants significantly limits treatment options. Therefore, the current study verified the Roche cobas® 6800/8800 System against the CAP/CTM system for the detection of HIV in EID and determined the HIVDR prevalence and profiles in infants <6 months, and how this affects current SA PMTCT and EID guidelines. The study comprised 642 DBS samples (235 HIV PCR positive, 193 HIV PCR negative and 214 HIV PCR indeterminate) previously tested on the CAP/CTM assay. Overall, 99.6% (234/235) CAP/CTM HIV PCR positive samples remained positive, while 99.5% (192/193) HIV PCR negative samples remained negative with the Roche cobas® 6800/8800 System. The HIV PCR indeterminate results as detected by the CAP/CTM decreased from 100% (214/214) to 8.4% (18/214) with the Roche cobas® 6800/8800 System. The Roche cobas® 6800/8800 System had a specificity of 99.5% and a sensitivity of 99.6%, but this decreased to 96.3% and 90.8% when HIV PCR indeterminate results were included. The kappa value increased from 0.5, which signifies moderate agreement, to 0.9, which is excellent agreement, when RFI from the CAP/CTM was excluded for result determination. The overall agreement between the two assays, taking only cycle threshold values into account, was 93.8%. As for HIVDR, mutations were detected in 42.9% (24/56) of infants <6 months. The most common non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation causing high-level resistance was K103N (21.4% [12/56]), followed by Y181C and the NRTI mutation, M184V, both in 8.9% (5/56) of infants. Also, major protease inhibitor (PI) mutations, M46L and V82A were detected in one case each (1.8%). In conclusion, the performance of the Roche cobas®6800/8800 System was comparable to the CAP/CTM; however, it detected fewer HIV PCR indeterminate results, thus potentially offering conclusive results in a larger proportion of infants. The detection of high levels of the NNRTI mutation, K103N, emphasises the need for constant surveillance since nevirapine is included as part of the SA PMTCT guidelines and the World Health Organization recommends that NNRTIs should be phased-out of as part of PMTCT once the resistance prevalence exceeds 10%.
Dissertation (MSc (Medical Virology))--University of Pretoria, 2021.
National Health Laboratory Services Trust and RDP UP
Medical Virology
MSc (Medical Virology)
Restricted

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23

Petersson, Christer. "Preschool children day-care, diseases and drugs : studies of risk factors for respiratory tract infections /." Lund : Dept. of Community Health Sciences, Lund University, 1994. http://books.google.com/books?id=Vs9sAAAAMAAJ.

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24

Redmond, Amy, Darshan Shah, Jason Pryor, and Stacy D. Brown. "Monitoring Buprenorphine and Metabolite Concentrations in Infant Cord Blood by LC-MS/MS." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/5279.

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25

Schäfer, Carola. "Analyse des Antimon-Resistenzmarkers ARM58 aus Leishmania infantum." Doctoral thesis, Universitätsbibliothek Leipzig, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-119243.

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Antimonpräparate sind seit über 60 Jahren der Standard zur Behandlung der Leishmaniose. Immer häufiger kommt es jedoch zum Therapieversagen durch resistente Erreger. In Indien sprechen über 60 % der erstmalig mit Antimonpräparaten behandelten Patienten nicht mehr auf die Therapie an (Sundar et al., 2000). Obwohl dies ein großes Problem darstellt, ist bisher wenig über die Resistenzmechanismen der Parasiten bekannt. Durch die Aufklärung dieser Mechanismen könnten zwei Hauptziele erreicht werden: i) Es könnten optimierte Medikamente entwickelt werden, die die Resistenzmechanismen der Parasiten umgehen. ii) Es könnten diagnostische Maßnahmen ergriffen werden, um vor Beginn einer Therapie deren Erfolgschancen zu kalkulieren. So würde man dem Patienten die starken Nebenwirkungen sowie die Kosten der Antimontherapie ersparen. Desweiteren könnte sofort mit einer wirkungsvollen Therapie begonnen und somit die Zeitspanne verkürzt werden, in der der infizierte Patient ein Reservoir für die weitere Transmission der Parasiten darstellt. In Vorarbeiten wurde durch genetische Komplementation das Gen LbrM20_V2.0210 (Lbr_0210) vorläufig identifiziert, das bei Überexpression Antimonresistenz vermittelt (Dissertation A. Nuehs, 2010). Diese Arbeiten wurden mit Leishmania braziliensis durchgeführt. Direkt benachbart befindet sich ein strukturell sehr ähnliches Gen, LbrM20_V2.0200 (Lbr_0200). Beide Gene wurden bei den vorangegangenen Sb(III)-Selektionen untersucht. Hierbei konnte ausschließlich Lbr_0210 als resistenzvermittelnd identifiziert werden. Datenbankrecherchen ergaben, dass es zu Lbr_0210 je ein direktes orthologes Gen in Leishmania infantum und Leishmania major gibt. Das Ziel des ersten Teils dieser Doktorarbeit war es, die resistenzvermittelnde Funktion des zu Lbr_0210 orthologen Gens aus L. infantum, LinJ34.0220, in unterschiedlichen Leishmania-Spezies zu verifizieren. Es war vor allem wichtig die Frage zu beantworten, ob das Gen auch im pathogenen Stadium des Parasiten, also in intrazellulären Amastigoten, Resistenz gegenüber Pentostam®, einem Standardmedikament, vermittelt. Im zweiten Teil dieser Arbeit sollte das Protein strukturell und zellbiologisch charakterisiert werden, um Hinweise auf den Resistenzmechanismus zu erhalten. Durch den Vergleich mit dem zu Lb_0200 orthologen Gen aus L. infantum, LinJ34.0210, sollten Hinweise auf die unterschiedlichen Aufgaben der Proteine gesammelt werden.

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Shoemaker, Griffin, Gloria Kwak, Gayatri Bala Jaishankar, and Karen E. Schetzina. "Prenatal Drug and Related Exposures in Infant Patients at Northeast Tennessee Pediatric Primary Care Clinic." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/5032.

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27

Shoemaker, Griffin, Gloria Kwak, Gayatri B. MD Jaishankar, and Karen E. MD MPH Schetzina. "Prenatal Drug and Related Exposures in Infant Patients of a Northeast Tennessee Pediatric Primary Care Clinic." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/18.

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Introduction: The prevalence of opioid abuse has increased throughout Northeast Tennessee. Subsequently, more infants are born drug-exposed or with Neonatal Abstinence Syndrome (NAS). According to the Tennessee Department of Health, hospitalizations for deliveries with maternal substance abuse tripled in Tennessee between 1999 and 2011. During this period, the inpatient hospitalization rate for NAS increased 11-fold. In 2017, there were 163 NAS cases reported in Northeast Tennessee. Depending on intrauterine and environmental exposures, there may be differences in health, growth, behavior, and development in infants. Our goal was to assess and explore those differences to help update education and care recommendations for pediatric primary care clinics. Methods: This cross-sectional study was set in a Northeast Tennessee pediatric clinic. 120 patients seen for a newborn visit between June 30, 2013 and July 1, 2014 were randomly selected. An additional sample of all infants with suspected drug exposure was identified for this period based on diagnosis codes. In total, 99 infants had no drug exposure and 62 were drug-exposed. An 83-item chart abstraction template was developed. Data was analyzed by SPSS. The chi-squared test and Mann-Whitney U test were used, with a critical value of p<0.05 to determine significance. The Bonferroni correction was applied to account for multiple comparisons. The research protocol was reviewed and approved by the Institutional Review Board of East Tennessee State University. Results: Of the 120 charts initially selected, 3.33% of infants were exposed to buprenorphine, 1.67% to methadone, 0.83% to marijuana, 0.83% to cocaine, and 1.67% to tobacco, 8.33% to benzodiazepine, and 1.67% to barbiturates during gestation. In total, 18.33% of infants had any drug exposure, 10.00% to any opiate, and 3.33% had a documented diagnosis of NAS in their chart. Prenatal drug exposure was significantly associated with multiple demographic factors as well as pediatric respiratory, behavioral, gastrointestinal, infectious disease, and cardiac conditions. Conclusions: Prenatal drug exposure was significantly associated with multiple pediatric complications. This illustrates the significance of addressing the increased incidence of prenatal drug exposure in Northeast Tennessee. Future multivariate analyses will attempt to control for potential confounders. This analysis is retrospective and exploratory, and any associations should be confirmed with a prospective study. A weakness of this study includes potential under-diagnosis of drug exposure and NAS due to lack of documentation in the EHR. Additional research will include further comparison of maternal and infant complications in drug-exposed and non-exposed infants. This will allow for a better understanding of the risks associated with maternal drug exposure. Findings from these research projects will be used to inform clinical initiatives for NAS in Northeast Tennessee.

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Holbrook, Landon T. "Generation and Delivery of Charged Aerosols to Infant Airways." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3979.

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The administration of pharmaceutical aerosols to infants on mechanical ventilation needs to be improved by increasing the efficiency of delivery devices and creating better ways of evaluating potential therapies. Aerosolized medicines such as surfactants have been administered to ventilated infants with mixed results, but studies have shown improvement in respiratory function with a much lower dose than with liquid instillation through an endotracheal tube (ETT). An aerosolized medicine must be transported through the ventilation tubing and deposit in the lungs to have the desired therapeutic response. This work has taken a systematic approach to (i) develop new devices for the efficient production of small sized charged pharmaceutical aerosols, (ii) adapt a lead device to an infant ventilation system, (iii) develop a novel breathing infant lung (BIL) in vitro model capable of capturing lung delivery efficiency in an infant without the need for human subjects testing, and (iv) evaluate the hypothesis that small sized charged pharmaceutical aerosols can improve drug delivery efficiency to the lungs of a ventilated infant. Three new devices were developed and screened for the efficient generation of small sized charged pharmaceutical aerosols, which were: wick electrospray, condensational vapor, and a modified vibrating mesh nebulizer in a streamlined low flow induction charger (LF-IC). Of these devices, only the LF-IC produced a small [mean(SD) = 1.6(0.1) micrometers] and charged (1/100 Rayleigh limit) aerosol at a pharmaceutically relevant production rate [mean(SD) = 183(9) micrograms per minute]. The LF-IC was selected as a lead device and adapted for use in an infant ventilation system, which produced an increase in in vitro lung filter deposition efficiency from 1.3% with the commercial system to 34% under cyclic ventilation conditions. The BIL model was first shown to produce a realistic pressure-volume response curve when exposed to mechanical ventilation. The optimized LF-IC was then implemented in the BIL model to demonstrate superior reduction in inspiratory resistance when surfactant was delivered as an aerosol compared to liquid instillation. For the delivery of an aerosolized medication, the lung deposition efficiency increased from a mean(SD) 0.4(0.1)% when using the conventional delivery system to 21.3(2.4)% using the LF-IC in the BIL model, a 59-fold increase. The charged aerosol produced by the LF-IC was shown to have more depositional loss in the LF-IC than an uncharged aerosol, but the charge decreased the exhaled fraction of aerosol by 17%, which needs additional study to achieve statistical significance. Completion of this work has produced a device that can achieve lung delivery efficiency that is 59-fold greater than aerosols from conventional vibrating mesh nebulizers in invasively ventilated infants using a combination of small particle size, synchronization with inspiration and appropriate charge. The BIL model produced in this work can be used to test clinically relevant methods of administering medications to infants and can be used to provide more accurate delivery estimates for development of new nebulizers and inhalers. The LF-IC developed in this work could be used for controlled and efficient delivery of aerosolized antibiotics, steroids, non-steroidal anti-inflammatories, surfactants, and vasodilators.

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Caudillo, Rachel Clare. "An evaluation of the impact of maternal substance abuse on infant and child attachment." CSUSB ScholarWorks, 2006. https://scholarworks.lib.csusb.edu/etd-project/2961.

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This study examined the impact and extent to which drugs and alcohol, consumed by mothers prenatally and perinatally, has affected their capacity to attach to their children. It examined the role the dependent variables measured (i.e. drug(s)/substance(s) abused, demographic information) played in the attachment process. Data was collected from mothers currently participating in the perinatal substance abuse treatment at the San Bernardino County Rialto program.

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Syed, Mohamed Ami Fazlin. "Pharmacokinetic and Pharmacodynamic Modeling of Antibiotics and Bacterial Drug Resistance." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-188306.

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Exposure to antibiotics is an important factor influencing the development of bacterial resistance. In an era where very few new antibiotics are being developed, a strategy for the development of optimal dosing regimen and combination treatment that reduces the rate of resistance development and overcome existing resistance is of utmost importance. In addition, the optimal dosing in subpopulations is often not fully elucidated. The aim of this thesis was to develop pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PKPD) models that characterize the interaction of antibiotics with bacterial growth, killing and resistance over time, and can be applied to guide optimization of dosing regimens that enhance the efficacy of mono- and combination antibiotic therapy. A mechanism-based PKPD model that incorporates the growth, killing kinetics and adaptive resistance development in Escherichia coli against gentamicin was developed based on in vitro time-kill curve data. After some adaptations, the model was successfully applied for similar data on colistin and meropenem alone, and in combination, on one wild type and one meropenem-resistant strain of Pseudomonas aeruginosa. The developed population PK model for colistin and its prodrug colistin methanesulfonate (CMS) in combination with the PKPD model showed the benefits for applying a loading dose for this drug. Simulations predicted the variability in bacteria kill to be larger between dosing occasions than between patients. A flat-fixed loading dose followed by an 8 or 12 hourly maintenance dose with infusion duration of up to 2 hours was shown to result in satisfactory bacterial kill under these conditions. Pharmacometric models that characterize the time-course of drug concentrations, bacterial growth, antibacterial killing and resistance development were successfully developed. Predictions illustrated how PKPD models based on in vitro data can be utilized to guide development of antibiotic dosing, with examples advocating regimens that (i) promote bacterial killing and reduce risk for toxicity in preterm and term newborn infants receiving gentamicin, (ii) achieve a fast initial bacterial killing and reduced resistance development of colistin in critically ill patients by application of a loading dose, and (iii) overcome existing meropenem resistance by combining colistin and meropenem

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Karami, Nahid. "Antibiotic resistance and fitness of Escherichia coli in the infantile commensal microbiota /." Göteborg : Department of Clinical Bacteriology, Göteborg University, 2007. http://hdl.handle.net/2077/4418.

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32

Potter, Susan M. "Effects of fetal cocaine and tobacco exposure on newborn information processing." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=42119.

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Approximately 10% of women use cocaine and 20% smoke cigarettes during pregnancy. Animal studies indicate that both cocaine and nicotine are neuroteratogenic agents, although findings with humans are inconsistent. Studies with human infants have been plagued by unreliable subject identification procedures, poor control over confounding factors, and invalid measures of CNS integrity. The literature on prenatal cocaine and nicotine use is reviewed and two studies are presented along with an intriguing case report. The effects of maternal prenatal cocaine use (Study 1) and two levels of cigarette smoking (Study 2) on newborn information processing ability were examined using an auditory habituation-recovery paradigm. Case-control designs were employed in which subjects were individually matched on a number of maternal and infant factors. Cocaine exposure was determined by newborn meconium analysis, urine analysis, and maternal self-report. Maternal smoking was determined by self-report and a variation of the bogus pipeline method. Fetal cocaine- and nicotine-exposure were associated with differential impairments in neonatal information processing. Cocaine-exposed newborns exhibited deficits on measures of habituation and recovery to novelty. Dose-response effects of nicotine-exposure were evident on measures of orientation and habituation, but recovery to novelty was not consistently affected. The results imply that fetal cocaine-exposure severely impairs neonatal auditory information processing ability, whereas fetal tobacco-exposure is associated with deficits in information-processing which may be secondary to impairments in arousal regulation. These auditory processing deficits may be related to the later language impairments reported in follow-up studies with cocaine-and tobacco-exposed infants. Following the two studies, a case is presented of an infant born to a woman who reported using large amounts of cocaine throughout pregnancy, although the infant's meco

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Oliveira, Adriano de. "Os recusados : uma experiência de moradia transitória infanto-juvenil no campo da saúde mental." Pontifícia Universidade Católica de São Paulo, 2015. https://tede2.pucsp.br/handle/handle/17103.

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Made available in DSpace on 2016-04-29T13:31:17Z (GMT). No. of bitstreams: 1 Adriano de Oliveira.pdf: 832466 bytes, checksum: 07d85b0ccad5a01ebc9de568a3cf40cd (MD5) Previous issue date: 2015-03-11
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
When studying a Children and Youth s Residencial Care, this research wanted to think critically about the nowadays practices of care and protection of children and adolescents in situation of vulnerability, personal or social risk. More specifically, are the ways to take care of and ways to protect, or, ultimately, ways of governing certain children and adolescents the focus of this work. For constituting the analysis field, we are guided by the genealogical work of Michel Foucault and Robert Castel. After, we take some aspects of history of practices directed at certain children and adolescents in the cern of social policies, in dialogue with Michel Foucault and Jacques Donzelot. Secondly, will be drawn some aspects of the history of types of government run by welfare policies directed to children and adolescents in Brazil, to finally present some ways of government operated from the compositions of social policies (Health and Welfare) with Justice. Finally, we make a brief passage through the history of drug policy in order to consider the context in which it proposes a residencial care service in the field of Mental Health, and from there follow its emergence in the city São Paulo, to finally make some notes on the institutional care as a care strategy. This wonders what cracks these new modalities of care are able to produce those modes of government, even heirs of punitive and stigmatizing practices as gifts in the history of assistance to children and adolescents in Brazil. We conclude that the Childern and Youth s Residencial Care says the urgent need to invent other ways of caring, the urgency to care and not imprison
Ao estudar uma Unidade de Acolhimento Infanto-juvenil, a presente pesquisa quis pensar criticamente a atualidade das práticas de cuidado e proteção direcionadas às crianças e adolescentes ditos em situação de vulnerabilidade social. Mais especificamente, são os modos de cuidar e modos de proteger, ou, em última análise, modos de governar certas crianças e adolescentes o foco deste trabalho. Para a constituição do campo de análise, fomos guiados pelos trabalhos genealógicos de Michel Foucault e Robert Castel. Num segundo momento, retomamos aspectos da história das práticas direcionadas à determinada população infanto-juvenil no bojo das políticas sociais, seguindo agora com Foucault e Jacques Donzelot. Em seguida, foram traçados alguns aspectos da história dos modos de governo executados pelas políticas assistenciais direcionadas à infância e adolescência no Brasil, para então apresentar alguns modos de governo operados a partir das composições das políticas sociais (Saúde e Assistência Social) com a Justiça. Por fim, fizemos uma breve passagem pela história das políticas de drogas no intuito de considerar o contexto em que se propõe uma unidade de acolhimento no campo da Saúde Mental, para daí acompanharmos sua emergência na cidade de São Paulo, e realizar alguns apontamentos sobre o acolhimento institucional como estratégia de cuidado. Perguntou-se que rachaduras essas novas modalidades de atenção são capazes de produzir naqueles modos de governo, ainda herdeiros das práticas punitivas e estigmatizantes tão presentes na história da assistência à infância e adolescência no Brasil. Podemos inferir que a UAI diz da urgência de se inventar outros modos de cuidar, da urgência de acolher e não aprisionar

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Lima, Bruna Roese de. "Detecção microbiana e de genes de resistência em ecossistemas da cavidade oral de pacientes infantis com necrose pulpar." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/128201.

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Alguns estudos caracterizaram a microbiota de canais radiculares de dentes decíduos com necrose pulpar como polimicrobiana, com predomínio de microrganismos anaeróbios. No entanto, nenhum estudo até o presente momento investigou a presença de genes de resistência a antimicrobianos em diferentes ecossistemas da cavidade oral de crianças. Este estudo tem por objetivo determinar a presença de espécies de Prevotella e do gene cfxa/cfxa2 associados à resistência à beta-lactâmicos, em diferentes ecossistemas orais de crianças com necrose pulpar. Vinte e sete crianças, que estavam sob cuidados odontológicos no Ambulatório de Clínica Infanto-Juvenil da Faculdade de Odontologia da UFRGS, e que apresentavam, pelo menos, um dente decíduo com necrose pulpar foram selecionados para este estudo. Foram coletadas amostras de saliva, biofilme supragengival, biofilme da câmara pulpar e do canal radicular de 32 dentes (27 posteriores e 5 anteriores). Após isolamento do DNA microbiano, a presença das bactérias Prevotella intermedia, Prevotella nigrescens, Prevotella tannerae e do gene cfxA/cfxA2 foi avaliada através do método de PCR. A amostra foi composta de pacientes com idade média de 5,5 anos (± 1,76). A taxa total de espécies de Prevotella foi de 29,1%, 25%, 21,8% e 32,29% em amostras de saliva, biofilme, câmara pulpar e canal radicular, respectivamente. As três espécies juntas não foram detectadas em todos os micro-ambientes do mesmo paciente, mas estavam presentes em 3,1% (n=1) de amostras do canal radicular. Prevotella nigrescens foi a bactéria mais frequentemente encontrada em todos os ecossistemas estudados. Foram observadas diferenças estatisticamente significativas em relação à presença de P. nigrescens em pelo menos um local e idade do paciente (teste t, p = 0,04). Também foi encontrada associação entre a presença desta bactéria, em pelo menos um local e uso de antimicrobianos (teste exato de Fisher, p = 0,014). A presença do gene de resistência à beta-lactâmicos, cfxA/cfxA2, foi testada em 12 pacientes da amostra, nos quatro micro-ambientes orais. Entre esses pacientes, 55,6% eram meninas, com idade média de 6 anos (± 2,5). Não foi detectada a presença deste gene em nenhuma amostra investigada. Os dados sugerem que a cavidade bucal de crianças com necrose pulpar apresenta presença diversificada de espécies de Prevotella em diferentes micro-ambientes orais. A ausência do gene cfxA/cfxA2 foi observada em todas as amostras investigadas. Estudos futuros, testando a presença de outros genes de resistência à beta-lactâmicos, são importantes para uma investigação abrangente.
Some studies characterized the microbiota of root canals of primary teeth with pulp necrosis as polymicrobial, with a predominance of anaerobic microorganisms. However, no study to date has investigated the presence of antimicrobial resistance genes in different ecosystems of the oral cavity of children. This study aims to determine the presence of Prevotella species and genes associated with resistance to beta-lactams in different oral enviroments of children with pulp necrosis. Twenty-seven children who were under dental care at the Children and Youth Clinic (Dental School, UFRGS, Porto Alegre, Brazil), and who had at least one primary tooth with pulp necrosis were selected for this study. Saliva, supragingival biofilm, pulp chamber biofilm and root canal biofilm were collected of 32 teeth (27 posterior and 5 anterior). After isolation of microbial DNA, the presence of Prevotella intermedia, Prevotella nigrescens, Prevotella tannerae and cfxA/cfxA2 gene were evaluated using the PCR. The sample consisted of patients with a mean age of 5.5 years (± 1.76). The total rate of Prevotella species was 29.1%, 25%, 21.8% and 32.29% in saliva samples, biofilm, pulp chamber and root canal, respectively. The three strains were not detected in all enviroments of the same patient, but were present at 3.1% (n = 1) of the root canal samples. Prevotella nigrescens was the most common bacteria in all oral enviroments. Statistical significant differences were observed for the presence of P. nigrescens at least one oral enviroment and age of the patient (t-test, p = 0.04). Also an association was observed, among the presence of these bacteria in at least one enviroment and use of antimicrobials (Fisher's exact test, p = 0.014). The presence of the resistance gene to beta-lactams, cfxA/cfxA2, was tested on 12 patients of the sample at all four oral enviroments. Among these patients, 55.6% were girls with a mean age of 6 years (± 2.5). Absence of this gene in the sample investigated was detected. The absence of cfxA/cfxA2 gene was observed in all the investigated samples. Future studies testing the presence of other resistance genes to beta-lactams, are important for a comprehensive investigation.

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Santos, Djanilson Barbosa dos. "Drug utilization profile and monitoring of adverse reactions in pediatric patients in the Hospital Infantil Albert Sabin." Universidade Federal do CearÃ, 2002. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=438.

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CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
INTRODUÃÃO: A populaÃÃo pediÃtrica se ressente dos poucos estudos que relacionem o perfil de utilizaÃÃo e ocorrÃncia de reaÃÃo adversa a medicamentos (RAM) em crianÃas hospitalizadas. OBJETIVOS: Descrever e avaliar a utilizaÃÃo de medicamentos e a ocorrÃncia de reaÃÃes adversas em pacientes pediÃtricos internados no Hospital Infantil Albert Sabin na perspectiva de contribuir para a reduÃÃo dos agravos decorrentes do uso de medicamentos em crianÃas hospitalizadas. METODOLOGIA: Estudo observacional longitudinal prospectivo, de seguimento de pacientes pediÃtricos hospitalizados por mais de 24 horas, em um hospital pÃblico de referÃncia. Pacientes de 1-173 meses de idade foram incluÃdos no estudo no perÃodo de 01 de agosto a 31 de dezembro de 2001. Foram realizadas visitas diÃrias Ã enfermaria para inclusÃo ou acompanhamento de pacientes; entrevistas com as mÃes por meio de um questionÃrio estruturado para levantar caracterÃsticas sÃcio demogrÃficas e antecedentes patolÃgicos dos entrevistados, familiares e das crianÃas, revisÃo das prescriÃÃes e dos prontuÃrios, conversa com mÃdicos, enfermeiras e farmacÃuticos quando necessÃrio. As suspeitas de RAM foram avaliadas pelo CEFACE conforme a metodologia recomendada pelo Programa de FarmacovigilÃncia da OMS. Na anÃlise estatÃstica foram utilizados o teste exato de Fisher, Student (t) e wilcoxon, considerando-se o nÃvel de significÃncia p < 0,05. RESULTADOS: Durante o perÃodo de estudo ocorreram 272 admissÃes predominantemente de crianÃas entre 1 e 23 meses de idade (47,4%); com mÃes de 1o grau completo ou incompleto de escolaridade (70,6%); famÃlias de renda familiar entre 1 e 5 salÃrios mÃnimos (61,0%). Dentre as crianÃas admitidas, 265 foram expostas a medicamentos no hospital (97%), recebendo em mÃdia 6,4 (1-18) medicamentos; a mÃdia de permanÃncia hospitalar foi de 14,7 (2-67) dias. O diagnÃstico mais freqÃente foi pneumonia (30%), a classe terapÃutica mais prescrita foi Antiinfecciosos de Uso SistÃmico (25,9%). Foram detectados 420 eventos adversos; destes, 33 foram classificados como RAM. A incidÃncia acumulada de RAM foi 12,5% (33/265) e a densidade de incidÃncia 0,8% (33/4042 pacientes-dia monitorizados). A pele foi o ÃrgÃo mais afetado (48,9%). O grupo terapÃutico mais implicado foi Antiinfecciosos de Uso SistÃmico (53,2%). As RAM foram leves ou moderadas em 97,9% dos casos, 57,5% ProvÃveis e a maioria foi dose independente (55,3%). Na anÃlise multivariada as chances de uma crianÃa hospitalizada apresentar uma RAM cresceram com o nÃmero de medicamentos administrados, entre aqueles do sexo masculino, com menor idade (< 2anos) e internada anteriormente de 3 a 4 vezes. CONCLUSÃO: Foi significativa a proporÃÃo de crianÃas menores de 2 anos usando medicamentos. A predominÃncia do uso de antimicrobianos Ã esperado e determina o perfil de RAM detectados. A identificaÃÃo de fatores de risco associado a RAM possibilita a seleÃÃo de subgrupos de pacientes pediÃtricos que requereriam maior racionalizaÃÃo terapÃutica e avaliaÃÃo da seguranÃa de medicamentos. PALAVRAS-CHAVE: farmacoepidemiologia; medicamentos; pediatria.

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Cruz, Félix Tiago Oliveira. "A dieta e os hábitos da grávida e as suas consequências na saúde materno-infantil." Master's thesis, [s.n.], 2014. http://hdl.handle.net/10284/4599.

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária
Introdução: Durante a gravidez ocorrem alterações de natureza variável na cavidade oral da gestante. Segundo a Academia Americana de Odontopediatria as doenças orais maternas, quando não tratadas, podem comprometer a saúde da mulher e da criança, daí, a necessidade de um conhecimento adequado sobre os fatores com influência na saúde materno-infantil, assim como, a necessidade da existência de normas padronizadas para a realização da consulta médico-dentária na grávida. Objetivos: Verificar, através da realização de uma revisão bibliográfica, as relações existentes entre a dieta e os hábitos da grávida e as suas modificações fisiopatológicas com as alterações gerais e orofaciais na criança. Pretende-se ainda, realçar a importância dos cuidados de saúde oral da grávida no sentido da otimização da saúde oral e geral materno-infantil. Materiais e métodos: Pesquisa bibliográfica efetuada nos motores de pesquisa da “MEDLINE/PUBMED”, “B-On” e “Science Direct” e nos arquivos da biblioteca da Faculdade de Ciências da Saúde da Universidade Fernando Pessoa, usando como termos de pesquisa: pregnancy AND gastrointestinal system, respiratory system, cardiovascular system, hormonal and imune system, oral health, oral pathologies, tobacco, drugs, alcohol and cafeine. Foram impostos limites de pesquisa, nomeadamente, artigos em língua inglesa publicados nos últimos 20 anos. Resultados: Nesta revisão foram verificadas associações positivas, embora de espetro variável, entre as variáveis estudadas: alterações fisiológicas da gravidez, a dieta e os hábitos da grávida e as consequências deletérias na saúde materno-infantil. Conclusão: A dieta e os hábitos maternos, assim como as alterações fisiológicas decorrentes da gravidez podem influenciar direta ou indiretamente o desenvolvimento da criança, no entanto, são necessários estudos adicionais que aportem maior força a estas associações. Salienta-se com este trabalho, a importância da consulta médico-dentária na gravidez, uma vez que, para além de proporcionar uma condição oral saudável na gestante, com repercussões positivas no desenvolvimento da criança, possibilita ainda a educação e motivação da grávida para importância da saúde oral no bebé. Por este motivo, o Médico dentista deve ser uma agente promotor de saúde, na medida em que deve aconselhar a futura mãe, entre outros aspetos, sobre a dieta do bebé e a higienização da sua cavidade oral. Introduction: During pregnancy many changes with variable nature occurs in the oral cavity of pregnancy women’s. According with American Academy of Pediatric Dentistry, maternal oral diseases, if not treated, could compromise the health of women and children whereby the necessity of an adequate knowledge about the factors that influence the maternal and child health as well as the necessity of the existence of standardized rules for the dental appointment pregnancy. Objectives: Investigate the relationship between diet and habits of pregnant and their pathophysiological changes to the general and orofacial changes in child relations. It´s also intended demonstrate the importance of oral health care of pregnant towards the optimization of oral and general health. Material and Methods: This search was made using "MEDLINE / PUBMED", "B-On" and "Science Direct" and the archives of the Health Sciences Faculty, Fernando Pessoa University Health Library, using as search terms: pregnancy AND pregnancy gastrointestinal system, respiratory system, cardiovascular system, hormonal and immune system, oral health, oral pathologies, tobacco, drugs, alcohol and caffeine. Search limits were imposed, namely, english language articles published in the last 20 years. Results: In this review, positive associations were observed between some variables: physiological changes of pregnancy, diet and habits of pregnant and deleterious consequences on maternal and child health, although this has a variable spectrum. Conclusion: The diet and maternal habits as well as the physiological changes caused by pregnancy could influence direct and indirectly the child´s grow, however additional studies are required to prove these associations. With this work, it´s noted the importance of dental appointment during pregnancy to provide a healthy oral condition in pregnant women with a positive impact on child grow and to educate and motivate the pregnant women for the oral health of the baby. For this reason, the dentist should be a promoter of health that should advice the future mother about the diet baby and hygiene of oral cavity.

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Magalhães, Lucas Sousa. "Caracterização fenotípica de Leishmania infantum obtidas de pacientes refratários ao tratamento com antimonial." Pós-Graduação em Biologia Parasitária, 2016. http://ri.ufs.br/jspui/handle/riufs/9806.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Visceral leishmaniasis (VL) is a serious infectious disease that if left untreated can lead to death. Chemotherapy is the main form of treatment and antimony are the drugs of first choice. Treatment efficacy is a consequence of the immunological profile of the patient, the pharmacokinetic properties of the drug and the inherent differences in each strain. The resistance of parasites to the antimonial and resistance to treatment is emerging worldwide. Few studies using clinical isolates of patients refractory to treatment seeking to understand the machinery of resistance. Thus, the present study aimed to characterize phenotypic components of clinical isolates of Leishmania (L.) infantum obtained from patients with LV refractory to treatment with Glucantime®. changes were evaluated ultrastructural front of the trivalent antimony (SbIII) and Action transport pumps related to drug efflux. In total, four strains were used: Two isolates treatment refractory patients and two isolates from patients responsive to treatment with antimony. The susceptibility of these strains was evaluated in vitro exposure to increasing concentrations of promastigotes SbIII and determination of median inhibitory concentration (IC50). In comparison, the IC50s of separate refractory patients are significantly greater than the IC50 of patients responsive isolated, showing an in vitro drug resistance profile. From these results, the concentration of 615 μM of SbIII was chosen to perform the experiments. This concentration proved to be toxic, but fully compatible with survival in all isolates. Then the isolates were subjected to transmission electron microscopy (TEM) after being exposed to 615 μM of SbIII for 48 hours. The two isolates from patients responsive to treatment demonstrated significant ultrastructural changes, with the presence of vacuolization, disorganization and cytoplasmic compression with increased eletrodensidade, and the strong presence of cells with intense loss eletrodense the cytoplasm, indicating incompatibility with life. While the two isolates from treatment refractory patients had preserved ultrastructure, with the presence of morphologically altered, compressed and electrodense cells, indicating the stress response. Finally, to assess the presence of transmembrane transport mechanisms related to drug efflux, the isolates were subjected to two protocols: using the fluorescent probe Rhodamine 123 with the channel blocker, verapamil hydrochloride, and the exposure to SbIII plus verapamil hydrochloride The results showed that MDR-1 type pumps are not related to the different in vitro resistance profiles to antimony in isolates from antimony-refractory patients. Together, the results of this study show that clinical refractory patients isolates have phenotypic characteristics that make her different behavior of isolates from patients responsive when exposed to antimony in vitro.
A leishmaniose visceral (LV) é uma doença infecciosa grave que se não tratada pode levar a morte. A quimioterapia é a principal forma de tratamento e os antimoniais são as drogas de primeira escolha. A eficácia do tratamento é uma consequência do perfil imunológico do paciente, das propriedades farmacocinéticas da droga e das diferenças intrínsecas de cada cepa. A resistência dos parasitos aos antimoniais e a refratariedade ao tratamento é mundialmente emergente. Poucos estudos utilizam isolados clínicos de pacientes refratários ao tratamento buscando compreender as maquinarias de resistência. Dessa forma o presente estudo teve como objetivo caracterizar componentes fenotípicos de isolados clínicos de Leishmania (L.) infantum obtidos de pacientes com LV refratários ao tratamento com Glucantime®. Foram avaliadas alterações ultraestruturais frente ao antimonial trivalente (SbIII) e ação de bombas de transporte relacionadas ao efluxo de droga. No total, foram utilizados quatro isolados: dois isolados de pacientes refratários ao tratamento e dois isolados de pacientes responsivos ao tratamento com antimonial. A susceptibilidade desses isolados foi avaliada in vitro com a exposição de promastigotas a concentrações crescentes de SbIII e determinação da concentração inibitória média (IC50). Quando comparadas, as IC50s dos isolados de pacientes refratários são significativamente maiores que as IC50s dos isolados de pacientes responsivos, mostrando um perfil de resistência a droga in vitro. A partir desses resultados, a concentração de 615 μM de SbIII foi escolhida para a execução dos experimentos. Essa concentração demonstrou ser tóxica, mas compatível com a sobrevivência em todos os isolados. Em seguida, os isolados foram submetidos a microscopia eletrônica de transmissão (MET) após serem expostos a 615 μM de SbIII por 48h. Os dois isolados de pacientes responsivos ao tratamento demonstraram alterações ultraestruturais significativas, com a presença de vacuolização, desorganização e compactação citoplasmática, com aumento da eletrodensidade, e a presença marcante de células com intensa perda de conteúdo eletrodenso do citoplasma, indicando incompatibilidade com a vida. Enquanto os dois isolados obtidos de pacientes refratários ao tratamento apresentaram algumas células morfologicamente alteradas, compactadas e eletrodensas, indicando resposta ao estresse. Por fim, para avaliar a presença de mecanismos de transporte transmembrana relacionados ao efluxo de droga, os isolados foram submetidos a dois protocolos: o uso da sonda fluorescente Rodamina 123 junto ao bloqueador de canais, cloridrato de verapamil, além do uso direto do verapamil na reversão da resistência durante a exposição ao SbIII in vitro. Os resultados obtidos demonstraram que bombas do tipo MDR-1 não estão relacionados aos diferentes perfis de resistência in vitro ao antimonial nos isolados de pacientes refratários. Juntos, os resultados encontrados no presente trabalho demonstram que isolados clínicos de pacientes refratários possuem características fenotípicas que tornam seu comportamento diferenciado dos isolados de pacientes responsivos quando expostos ao antimonial in vitro.
São Cristóvão, SE

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Bailey, Beth A., Judy G. McCook, Alexis Hodge, and Lana McGrady. "Infant Birth Outcomes Among Substance Using Women: Why Quitting Smoking during Pregnancy Is Just as Important as Quitting Illicit Drug Use." Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etsu-works/7173.

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Poor birth outcomes are associated with illicit drug use during pregnancy. While prenatal cigarette exposure has similar effects, cessation of illicit drug use during pregnancy is often prioritized over cessation of smoking. The study goal was to examine the impact of pregnancy tobacco use, relative to use of illicit drugs, on birth outcomes. Women were recruited at entry to prenatal care, with background and substance use information collected during pregnancy. Urine drug screens were performed during pregnancy, and the final sample (n = 265) was restricted to infants who also had biologic drug testing at delivery. Participants were classified by pregnancy drug use: no drugs/no cigarettes, no drugs/cigarette use, illicit drugs/no cigarettes, and illicit drugs/cigarette use. Groups differed significantly on infant birthweight, but not gestational age at delivery after control for confounders including background and medical factors. Among women who smoked, the adjusted mean birthweight gain was 163 g for those not using hard illicit drugs, while marijuana use had no effect on birth weight beyond the effect of smoking cigarettes. Women who used hard illicit drugs and did not smoke had an adjusted mean birthweight gain of 317 g over smokers. Finally, women who refrained from hard illicit drugs and smoking had a birthweight gain of 352 g. Among substance using pregnant women, smoking cessation may have a greater impact on birthweight than eliminating illicit drug use. Intervention efforts should stress that smoking cessation is at least as important to improving pregnancy outcomes as abstaining from illicit drug use.

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Hiraki, Patricia Yuko. "Estudo comparativo do uso de betabloqueador e corticosteroide oral no tratamento do hemangioma infantil." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5132/tde-20022018-132655/.

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INTRODUÇÃO: Hemangioma Infantil (HI) é o tumor vascular mais comum da infância. Em 1992 a International Society for the Study of Vascular Anomalies (ISSVA) definiu o hemangioma infantil como tumor benigno de células endoteliais, com características clínicas, radiológicas e imuno-histoquímicas específicas. A origem do HI ainda é desconhecida. É sabido que apresentam potencial involutivo espontâneo e que o tratamento é indicado em 10% a 20% dos casos, podendo ter caráter emergencial ou eletivo. As indicações emergenciais compreendem situações de ameaça à função ou vida. As indicações eletivas são reservadas aos casos de hemangiomas localizados em áreas que podem levar à deformidade e/ou cicatriz permanente, quando apresentam complicações locais ou pequenas lesões em áreas expostas, podendo o tratamento ser clínico ou cirúrgico. A terapêutica medicamentosa tem sido a rotina e historicamente a opção mais utilizada foi o corticosteroide, cuja a eficácia é variável e os eventos adversos são frequentes. Em 2008 uma descoberta fortuita introduziu os betabloqueadores como nova opção para o tratamento do HI, com resultados estáveis e posteriores evidências clínicas do benefício da droga no tratamento do HI. Neste contexto, propôs-se avaliar o uso do propranolol, quantificando sua eficácia, segurança e incidência de eventos adversos, comparando-se ao uso da prednisolona (PRED). MÉTODO: Estudo intervencionista prospectivo randomizado com 50 portadores de HI, atendidos no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Os pacientes selecionados tinham idade inferior a 2 anos e indicação eletiva de tratamento. Os indivíduos incluídos foram aleatoriamente alocados em 2 grupos, sendo o primeiro grupo de tratamento com prednisolona e o outro de tratamento com propranolol (PROP), ambos por via oral, por 2 meses. Os pacientes foram seguidos semanalmente para mensuração de parâmetros clínicos incluindo peso, pressão arterial (PA), frequência cardíaca (FC) e saturação de oxigênio, além de avaliação objetiva da ocorrência de eventos adversos. A resposta ao tratamento foi avaliada de forma quantitativa por meio de medidas diretas da lesão e por 3 avaliadores independentes segundo critérios de melhora do aspecto clínico geral, volume, cor e envolvimento funcional. Os eventos adversos foram avaliados quanto a sua incidência e gravidade, utilizando-se a classificação do Common Terminology Criteria for Adverse Events. RESULTADOS: Vinte e seis pacientes foram alocados no grupo PRED e 24 no grupo PROP. Da casuística 37 indivíduos completaram as 8 semanas de seguimento. Em 8 casos houve interrupção precoce do tratamento em função de eventos adversos, em 1 caso por falha terapêutica e em 4 casos houve perda de seguimento. A idade média no grupo PRED foi de 6,46 meses e no grupo PROP de 7,25 meses. O gênero feminino foi predominante em ambos os grupos. A face foi a localização anatômica mais acometida, seguido do tronco. A resposta ao tratamento foi efetiva e sem distinção entre os grupos, com redução significativa das medidas avaliadas. Quanto as avaliações clínicas de acordo com o coeficiente de correlação interclasses, houve concordância interna excelente entre os avaliadores. As notas atribuídas para os pacientes mostraram melhora com o tratamento e no quesito cor mostrou-se diferença significativa em favor do grupo PROP. Quanto aos parâmetros clínicos mensurados, o percentil de peso mostrou elevação progressiva no grupo PRED sendo a diferença significativa em relação ao grupo PROP. A diferença nas medidas de PA sistólica entre os grupos foi significativa e a análise multivariável evidenciou uma elevação significativa no grupo PRED ao passo que no grupo PROP não houve alteração dos níveis pressóricos. A avaliação da FC revelou um significativo declínio no grupo PROP na 6º semana, não se mantendo no restante do período. Não foram identificadas alterações nas medidas de saturação de oxigênio. Quanto a incidência os eventos adversos (EA) a diferença entre os grupos foi significativa. No grupo PRED 22 pacientes apresentaram 35 EA sendo os mais frequentes o aspecto cushingoide, elevação da PA e infecções. No grupo PROP 10 pacientes apresentaram 10 EA incluindo hipotensão e distúrbios respiratórios. Quando a gravidade dos EA foi avaliada não foram observadas diferenças. CONCLUSÃO: Prednisolona e propranolol foram igualmente efetivos em reduzir o tumor. Considerando-se os eventos adversos, o uso do propranolol se mostrou como tratamento mais tolerável em relação ao uso do corticosteroide
INTRODUCTION: Infantile hemangioma (HI) is the most common vascular tumor of childhood. In 1992 the International Society for the Study of Vascular Anomalies (ISSVA) defined infantile hemangioma as a benign endothelial cell tumor with specific clinical, radiological and immunohistochemical characteristics. The origin of HI is still unknown. It is known that they have spontaneous involutive potential and that the treatment is indicated in 10% to 20% of the cases, and it can be emergency or elective. Emergency indications include life threatening situations. Elective indications are reserved for cases of hemangiomas located in areas that may lead to permanent deformity and/or scarring, when they present local complications or small lesions in exposed areas, and this treatment may be clinical or surgical. Drug therapy has been the routine and historically the most widely used option was the corticosteroid, whose efficacy is variable and the adverses events are frequent. In 2008 a fortuity finding introduced beta-blockers as a new option for HI treatment, with stable results and subsequent clinical evidence of drug benefit in the treatment of HI. In this context, it was proposed to evaluate the use of propranolol, quantifying its efficacy, safety and incidence of adverse events, compared to the use of prednisolone. METHODS: Prospective randomized interventional study with 50 patients with HI from the \"Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo\". The patients selected were younger than 2 years and had an elective indication of treatment. Patients included were randomly allocated into 2 groups, the first group being treated with predinisolone (PRED) and the other with propranolol (PROP), both orally, for 2 months. Patients were followed weekly to measure clinical parameters including weight, blood pressure (BP), heart rate (HR) and oxygen saturation, as well as an objective evaluation of the occurrence of adverse events. The response to treatment was quantitatively assessed by means of direct measures of the lesion and by 3 independent evaluators according to criteria of improvement of general clinical appearance, volume, color and functional involvement. Adverse events were evaluated for their incidence and severity, using the classification of the Common Terminology Criteria for Adverse Events. RESULTS: Twenty-six patients were allocated to the PRED group and 24 to the PROP group. Overall, 37 patients completed the 8-week follow-up. In 8 cases there was an early interruption of treatment due to adverse events, in 1 case due to therapeutic failure and in 4 cases there was loss of follow-up. The mean age in the PRED group was 6.46 months and in the PROP group of 7.25 months. The female gender was predominant in both groups. The face was the most affected anatomic location, followed by the trunk. The treatment response was effective and without distinction between groups, with a significant reduction of the measures evaluated. Regarding the clinical evaluations according to the interclass correlation coefficient, there was excellent internal agreement among the evaluators. The scores attributed to the patients showed improvement with the treatment and in the item color there was a significant difference in favor of the PROP group. Regarding the clinical parameters measured, weight percentile showed progressive elevation in the PRED group, presenting significant difference in relation to the PROP group. The difference in systolic BP measurements between groups was significant and multivariate analysis showed a significant increase in the PRED group, whereas in the PROP group there was no change in pressure levels. The HR evaluation revealed a significant decline in the PROP group in the 6th week, not remaining in the remainder of the period. No changes in oxygen saturation measurements were identified. Regarding the incidence and adverse events (AE), the difference between the groups was significant. In the PRED group 22 patients presented 35 AEs, the most frequent being cushingoid appearance, elevated BP and infections. In the PROP group 10 patients presented 10 AEs including hypotension and respiratory disorders. When the severity of AE was assessed, no differences were observed. CONCLUSION: Prednisolone and propranolol were equally effective in reducing the tumor. Considering the adverse events, the use of propranolol was shown as a more tolerable treatment in relation to corticosteroid use

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Kinkead, James Robert H. "Study of the molecular regulation of trypanosomatid phosphofructokinases as drug targets." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31144.

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The trypanosomatid parasites T. brucei, T. cruzi and Leishmania spp. are responsible for the ‘neglected diseases’ Human African Trypanosomiasis, Chagas disease and Leishmaniasis respectively. In their human infective form in the bloodstream all three trypanosomatid parasites rely heavily on glycolysis for ATP production. Phosphofructokinase (PFK) catalyses the third step of the glycolytic pathway in all organisms using aerobic respiration. It facilitates the phospho transfer from ATP to fructose 6-phosphate (F6P) to make the products fructose 1,6- bisphosphate (F16BP) and ADP. RNAi knockout of T. brucei PFK has shown the enzyme is essential for survival of the bloodstream form parasites. Trypanosomatid PFKs have a unique set of structural and regulatory differences compared to the mammalian host enzyme. These differences, coupled with the availability of trypanosomatid PFK crystal structures present an opportunity for the structure-based design of specific inhibitors against the enzyme. Here we present an enzymatic characterisation of recombinant PFKs from T. brucei, T. cruzi and Leishmania infantum trypanosomatids, their regulation by the allosteric activator AMP, and their inhibition by drug-like inhibitor compounds. Inhibitor compounds (‘CTCB compounds’) were designed against T. brucei PFK with the aim of developing novel treatments against Human African Trypanosomiasis (HAT). We describe the testing, ranking and biophysical characterisation of these compounds as part of a Wellcome Trust Seeding Drug Discovery program. We found that CTCB inhibitor compounds bound to an allosteric pocket unique to trypanosomatid PFKs. We show that the compounds are specific; neither competing with the natural substrates ATP or F6P nor inhibiting the human PFK enzyme. We describe the development and testing of highly potent and specific low molecular weight PFK inhibitors that translate to both killing of cultured T. b. brucei parasites and a cure of stage I HAT in mice models. We describe the tight, 1:1 binding of these compounds with trypanosomatid PFKs, and the thermodynamic characteristics of binding through various biophysical assays. We also show the unprecedented characterisation of the reverse PFK reaction by trypanosomatid and human forms of the enzymes. We found that PFK can also carry out the reverse enzymatic reaction, under physiologically relevant concentrations of ADP and F16BP to produce F6P and ATP. We show that the reverse reaction is also subject to allosteric regulation by AMP, and can be inhibited by the CTCB compounds with a similar potency to the forward reaction. Finally, we describe the mechanism of allosteric activation by AMP and inhibition by the drug-like compounds against trypanosomatid PFKs.

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Griesel, H. A. "Comparison of the trough levels of two vancomycin formulations in a selected preterm infant population." Thesis, University of the Western Cape, 2014. http://hdl.handle.net/11394/3982.

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>Magister Scientiae - MSc
The aim of this study was to compare the trough plasma levels of Aspen-Vancomycin® (AV); and Sandoz-Vancocin CP® (SV) in premature infants with suspected Methicillin Resistant Staphylococcus aureus (MRSA) infection. The study was designed as a prospective, double blind, randomised trial involving male and female premature infants admitted in the Neonatal Intensive care Unit (NICU) at Netcare Blaauwberg and N1-city Hospitals for treatment of suspected MRSA-infection between April 2012 and June 2013. The inclusion criteria were: 29-35 weeks postmenstrual age (PMA), informed and written consent from parents of each premature infant enrolled in the study. Blood samples (0.3-0.4ml) were collected for renal function test and vancomycin trough levels determination. Blood samples for vancomycin trough level assay were collected thirty minutes prior to the administration of the third dose of vancomycin. Statistical analysis was performed and estimation was made giving an indication of how many infants will be needed to make the study statistically significant. Wilcoxon Two-Sample test was performed to determine the p-values and Spearman correlation coefficients were used to determine the correlation between trough levels and variables. P-values < 0.05 were considered significant. A total of 19 premature infants met with study criteria, 10 (5 females and 5 males) received AV and 9 (6 females and 3 males) receive d SV. There was no statistical significant difference between the demographic (GA, BW, PMA, PNA, weight at trial entry, height at trial entry) and biological (albumin, serum creatinine concentration and glomerular filtration rate) parameters of the premature infants in the AV and SV group. There were no statistical significant difference between trough level 1 of AV and SV, although trough level 1 had a lower trend in the SV group (p=0.118). No AV trough level 1 was below the minimum effective concentration (<5μg/ml). It was found that 30% of AV trough level 1 was within the therapeutic range (5-10μg/ml) and 70% of AV trough level 1, were above minimum toxic concentration (>10mg/l). It was found that 22.2% of SV trough level 1 was below minimum effective concentration, 44.4% of SV trough level 1 was within therapeutic range and 33.3% of trough level 1 was above minimum toxic concentration. No correlation was found between trough level 1 and the demographic and biological parameters of the premature infants in the AV group. SV had a positive correlation with GA, BBW, PMA and a negative correlation with PNA

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Araújo, Sandra Hernandez Morais de. "Perfil farmacoterapêutico de adolescentes usuários de um centro de atenção psicossocial álcool e drogas infanto juvenil do estado de Goiás." Universidade Federal de Goiás, 2017. http://repositorio.bc.ufg.br/tede/handle/tede/7570.

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Introduction: The use of Psychoactive Substances (PS) brings problems in several areas of the subject's life such as: health, psychological and social. Epidemiological studies show that it is in the passage from childhood to adolescence that the use begins. In Brazil, the treatment is preferentially done in the Centers of Psychosocial Care and in them are offered psychosocial and pharmacological interventions and the combination of them. Pharmacological interventions can be used to stabilize, detoxify, ameliorate withdrawal symptoms and prevent relapse. The pharmacist plays an important role in the safe and effective use of medicines in children and adolescents, since it can prevent identifying, evaluating and intervening in problems related to pharmacotherapy. Objective: to analyze the use of drugs by users of the Psychosocial Care Center Alcohol and Drugs Infanto Juvenil 24 hours (CPCAD adi III). Methodology: an analytical and quantitative cross-sectional study, carried out by reviewing medical records. The medical records of users who were younger than 18 years of age and with prescription of medicines were included and the medical records that were not filled out were excluded. Potential drug interactions (PDI) were analyzed using the Micromedex® and Medscape® database. Descriptive and bi-and multivariate logistic regression analyzes were performed considering a statistically significant relationship p≤0.5. Results: Of the 159 records used in the study, 71.7% were male subjects with mean age of 16 ± 1.9 years, incomplete elementary schooling (88%) and the search for treatment occurred in 55, 3% by judicial measure. Among the diagnostic hypotheses, the most frequent were mental and behavioral disorders due to the use of multiple drugs and the use of other psychoactive substances (F19) 34.9% and mental and behavioral disorders associated with the use of cannabinoids (F12) With 17.2%. The age of first use of SP was on average 12.4 ± 1.90 years. The most used PS was Cannabis (37.2%). The most prescribed drugs were the N03A (antiepileptic) 39.94% and N05A (antipsychotic) 34.83%% groups. A total of 815 PDI were found per type of interaction, 352 drugcannabis, 139 drug-ethanol, 125 drug-foods, 99 drug-tobacco, 83 drug-drug, and 17 drug-cocaine. Regarding the severity of the PDI found, 59.4% were moderate, 23.8% were secondary, 15.7% were serious and 1.1% were contraindicated. The drugs that presented the most PDI were chlorpromazine (32.3%) and diazepam (19.6%). Conclusion: the adolescents were the majority of males, the diagnostic hypothesis that had the highest frequency was that of mental and behavioral disorder due to the use of SPA (F-19). The use of PS was on average at 12 years of age and the most consumed PS was marijuana. The most commonly prescribed drugs were valproic acid (30.63%) and chlorpromazine (20.72%). It was found of 815 PDI with 59.4% classified as moderate. The factor involved in polypharmacy was total PDI and among the factors involved in the occurrence of total PDI were: being studying and the amount of diagnostic hypothesis. In view of the high PDI index, the relationship with polypharmacy and a high number of diagnostic hypotheses, it is necessary to increase the attention of health professionals regarding the topic and the development of protocols to support decision making.
Introdução: o uso de Substâncias Psicoativas (SPA) acarretam problemas em diversas áreas da vida do sujeito tais como: na saúde, psicológicos e sociais. Estudos epidemiológicos mostram que é na passagem da infância para a adolescência que se inicia o uso. No Brasil, o tratamento é feito preferencialmente nos Centros de Atenção Psicossocial e neles são ofertadas intervenções psicossociais e farmacológicas e a combinação delas. As intervenções farmacológicas podem ser utilizadas para estabilizar, desintoxicar, melhora dos sintomas de abstinência e evitar recaídas. O farmacêutico exerce papel importante na utilização segura e eficaz de medicamentos em crianças e adolescentes, pois o mesmo pode prevenir identificar, avaliar e intervir nos problemas relacionados à farmacoterapia. Objetivo: analisar a utilização de medicamentos por usuários do Centro de Atenção Psicossocial Álcool e Drogas Infanto Juvenil 24 horas (CAPS adi III). Metodologia: estudo transversal analítico e quantitativo, realizado por meio da revisão de prontuários. Foram incluídos os prontuários dos usuários que eram menores de 18 anos de idades e com prescrição de medicamentos e foram excluídos os prontuários que não estavam devidamente preenchidos. As potenciais interações medicamentosas (PIM) foram analisadas por meio do banco de dados Micromedex® e Medscape®. Foram realizadas análises descritivas e de regressão logística bi e multivariada considerando relação estatística significante p≤0,5. Resultados: dos 159 prontuários utilizados no estudo, 71,7% eram sujeitos do sexo masculino com a média de idade de 16 ± 1,9 anos, escolaridade ensino fundamental incompleto (88%) e a busca pelo tratamento deu-se em 55,3% por medida judicial. Dentre as hipóteses diagnósticas, as que apresentaram maior proporção foram os transtornos mentais e comportamentais decorrentes do uso de múltiplas drogas e do uso de outras substâncias psicoativas (F19) 34,9% e transtornos mentais e comportamentais associados com o uso de canabinóides (F12) com 17,2%. A idade do primeiro uso de SPA foi em média de 12,4 ±1,90 anos. A SPA mais utilizada foi a Cannabis (37,2%). Os medicamentos mais prescritos foram os grupos N03A (antiepilépticos) 39,94% e N05A (antipsicóticos) 34,83%%. Foram encontradas 815 PIM e por tipo de interação, foram encontradas 352 medicamento-cannabis, 139 medicamento-etanol, 125 medicamentoalimento, 99 medicamento-tabaco, 83 medicamento-medicamento e 17 medicamento-cocaína. Em relação a gravidade das PIM encontradas foram 59,4% moderadas, 23,8% secundárias, 15,7% graves e 1,1% contraindicado. Os medicamentos que mais apresentaram as PIM foram a clorpromazina (32,3%) e o diazepam (19,6 %). Conclusão: os adolescentes eram a maioria do sexo masculino, a hipótese diagnóstica que teve a maior frequência foi a de transtorno mental e comportamental devido ao uso de SPA (F-19). O uso de SPA foi em média aos 12 anos de idade e a SPA mais consumida foi a maconha. Os medicamentos mais prescritos foram: ácido valpróico (30,63%) e clorpromazina (20,72%). Encontrou-se de 815 PIM com 59,4% classificadas como moderada. O fator envolvido na polifarmácia foi o total de PIM e dentre os fatores envolvidos na ocorrência do total PIM, foram: estar estudando e a quantidade de hipóteses diagnóstica. Diante do alto índice de PIM, a relação com polifarmácia e alto número de hipóteses diagnósticas, faz-se necessário maior atenção dos profissionais de saúde quanto ao tema e desenvolvimento de protocolos para suporte na tomada de decisão.

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Sarmento, Naelka. "Comunidades e fatores de virulência bacterianos na cavidde bucal de pacientes infantis com infecções endodônticas em dentes decíduos." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/179863.

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A presente tese teve como objetivo realizar a descrição dos microrganismos que já foram isolados ou detectados em infecções endodônticas de dentes decíduos em pacientes infantis por meio de uma revisão sistemática, além de avaliar a composição bacteriana e a presença de genes de resistência a antibióticos em amostras de saliva (S), biofilme supragengival (SB), dentina (D) e câmara pulpar (RC) de dentes decíduos com infecções endodônticas. No Capítulo 1, realizou-se revisão sistemática em bancos de dados eletrônicos, tendo sido incluídos estudos clínicos que avaliaram presença de microrganismos em dentes decíduos com infecções endodônticas, por meio de análise microbiológica com cultivo ou de métodos moleculares. Foi realizada análise descritiva dos dados. A análise identificou 44 títulos, sendo revisados, na íntegra, 17 artigos. Foram selecionados 8 estudos clínicos, de acordo com os critérios de inclusão determinados. Por meio de busca manual, foram selecionados 2 artigos adicionais, totalizando 11 artigos excluídos desta revisão. Nos oito estudos clínicos incluídos na revisão sistemática, a identificação dos microrganismos envolvidos nas infecções endodônticas foi realizada por meio de várias técnicas como: cultura microbiológica, hibridização DNA-DNA, PCR e suas variações, clonagem, sequenciamento e pirossequenciamento, confirmando a diversidade de microrganismos envolvidos nas infecções endodônticas de dentes decíduos. A análise dos dados sugere que as infecções endodônticas em dentes decíduos são causadas por múltiplas combinações de espécies de micro-organismos, confirmando a sua natureza polibacteriana. No Capítulo 2, amostras de S, SB, D e RC foram coletadas de pacientes infantis com infecções endodônticas. O perfil das comunidades microbianas foram obtidos por meio da análise da região espaçadora intergênica relacionada aos genes 16S e 23S rRNA (PCR-RISA). Determinaram-se e índices de riqueza, dominância, índice de Shannon, índice de Chao-1 (alfa-diversidade) e análise multivariada de conglomerados (método UPGMA e índice de Similaridade de Bray-Curtis) e análise de coordenadas principais (PCoA) (beta-diversidade). Há um baixo grau de agrupamento entre as amostras de S, BS, D e RC, obtidas de um mesmo participante. Se presentes, os agrupamentos acontecem para sítios contíguos, mas com baixo percentual de similaridade. Amostras de um mesmo ecossistema obtidas de diferentes participantes abrigam comunidades bacterianas distintas, com baixa similaridade. Não parece haver uma relação entre a presença de um sinal/sintoma clínico e acréscimo no perfil de similaridade das comunidades bacterianas em RC. Não foram observadas diferenças estatisticamente significativas entre os índices de alfa-diversidade (riqueza, dominância, Shannon e Chao-1) entre S, SB, D e RC. O uso prévio de antibióticos não modificou os resultados de alfa diversidade ou de beta diversidade obtidos. No Capítulo 3, verificou-se a distribuição dos genes de resistência bacteriana aos principais grupos de antibióticos em S, SB, D, e RC dentes decíduos em pacientes infantis com infecções endodônticas e também de amostras de saliva dos responsáveis (R) por meio de PCR para os genes cfxA/cfxA2, blaTEM, blaZ, ampC, mecA, mefA, ermB, ermC, tetQ, tetM, tetW, linB, lsaB. Realizou-se análise estatística descritiva e análise multivariada de conglomerados (método UPGMA e índice de Similaridade de Bray-Curtis). Dos pacientes selecionados, 3/8 utilizaram antibiótico previamente à coleta. Nenhum gene de resistência foi observado em todos os ecossistemas de um mesmo participante. Os genes mais frequentemente detectados foram os genes de resistência à tetraciclina tetQ e tetW. Não foram detectados nas amostras os genes ampC, mecA, lnuB e lsaB. A presença simultânea de um gene em dois nichos ocorre em ecossistemas contíguos. Não se observa um comportamento uniforme quanto ao perfil de agrupamento de diferentes amostras de um mesmo participante, e nem entre as amostras de saliva do participante infantil (S) e seu responsável (R). Há múltiplos perfis de distribuição de genes de resistência a agentes antimicrobianos em amostras de ecossistemas bucais contíguos em um mesmo paciente portador de infecção endodôntica. A análise conjunta dos dados permite concluir que cada um dos ecossistemas da cavidade bucal de crianças portadoras de infecções endodônticas avaliado apresenta espécies bacterianas e fatores de virulência distribuídos de forma única e distintas, a partir de uma perspectiva de análise de diversidade.
This thesis aimed assessing information on the bacteria that were isolated/detected in teeth with endodontic infections from infant patients through a sistematic review of the literature. Furthermore, the bacterial composition and the presence of resistance genes to antimicrobial agents was determined in saliva (S), in supragengival biofilm (SB), in dentine (D) and in pulp cavity (RC) samples. In the Chapter 1, a sistematic review was conducted in electronic databasis. Clinical studies that evaluated the presence of microorganims in primary teeth with endodontic infections through culture and molecular methods were included. Fourty-four titles were selected and 17 articles were fully revised. Eight clinical studies were selected for data extraction. Two articles were included following the hand search. According to the data analysis, microbial identification was performed by culture, DNA-DNA hybridization, PCR, cloning and sequencing and next-generation sequencing methods. A high diversity in the microbial components identificated/detected was reported. Endodontic infections in primary teeth are polymicrobial, with a multi-species consortia. In the Chapter 2, the S, SB, D and RC samples were collected from infanti patients with endodontic infections. The ribossomal intergenic spacer analysis (PCR-RISA) for the 16S-23S rRNA genes interspacer region was employed to determine the bacterial fingerprint for each sample. Metrics for alfa and beta diversity were employed, such as richness, dominance, Shannon Index, Chao-1 Index, cluster analysis (UPGMA, Bray-Curtis Index) and principal coordenate analysis (PCoA). There was a low grouping profile for shared samples of S, BS, D and RC from the same participant. When detected, clustering behavior was observed for contiguous sites, with low percentual of similarity between them. Samples from the same site but from different subjects harboured distinct bacterial communities, with low similarity. No clinical sign/symptom was detected as a grouping factor for RC sample from different subjects. No statistical difference was detected for the alfa-diversity indexes among S, SB, D and RC. The previous exposition to antimicrobial agentes has no effect over the alfa- and beta-diversity indexes. In the Chapter 3, the distribution of bacterial genes for antimicrobial resistance in S, SB, D and RC was determined in samples from children with endodontic infections and their relatives (R) by PCR. The presence of the genes cfxA/cfxA2, blaTEM, blaZ, ampC, mecA, mefA, ermB, ermC, tetQ, tetM, tetW, linB, and lsaB was detecte in the samples. Descriptive statistical analysis and multivariate anlysis (cluster analyisis, UPGMA and Bray-Curtis similarity index) were carried out. Three out of 8 patients had antimicrobial agents previously to the apointment. No resistance gene was shared by all envirnments in the same participant. The most frequently detected genes were tetQ and tetW. The genes ampC, mecA, lnuB, and lsaB were not detected in any the samples. The same gene was detected only in two contiguous niches. Clustering analysis revealed no grouping pattern among the samples, despite they were or not from the same participant or his/her relative. Multiple profiles of resistance genes distribution were detected in the oral cavity samples from infant participants. The oral cavity in children with endodontic infection is a complex environment that harbours unique bacterial communities profiles and a distinct distribution of resitance genes to antimicrobial agents, considering an ecological perspective.

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Braga, Rodolpho de Campos. "Estratégias integradas em Química Medicinal para a identificação de novos compostos bioativos contra Leishmania infantum." Universidade Federal de Goiás, 2015. http://repositorio.bc.ufg.br/tede/handle/tede/6276.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
In view of the alarming scenario of visceral leishmaniasis in Brazil and in the world, especially due to the increasing number of cases of drug resistance and due to the few drugs available, it is essential to search for new therapeutic alternatives for this parasitosis. The complete sequencing of the genome of the main species of Leishmania opened great possibilities in understanding these diseases and initiated the post-genomic era of drug discovery against kinetoplastids. In this context, the enzyme 14 a-sterol demethylase (CYP51) of Leishmania is especially involved in the biosynthesis of ergosterol, the main sterol membrane and vital to the parasite. Furthermore, it was recently shown that inhibition of CYP51 of L. donovani is essential for the growth of the parasite, and therefore, is a validated target for the development of new leishmanicidal drugs. The aim of this work was the development and implementation of integrated strategies in medicinal chemistry to identify new bioactive compounds against L. infantum using CYP51 enzyme as molecular target. For this, we compiled, integrated and prepared the largest publicly available data sets related to CYP51 and phenotypic assays for Leishmania infantum amastigotes. Virtual screening models (VS) were constructed and extensively validated and applied to filter over 1 million of commercial compounds. The best models for VS were ROCS (LBDD) and pharmacophore (SBDD), with an area under the ROC curve (AUC) values of 0.86-0.90. The consensus between the two models had greater performance, with AUC of 0.93 and high recognition ability active ligands in the top 1% hits. Quantitative structure-activity relationship (QSAR) models robust and predictive were generated and validated for L. infantum (amastigote forms). The models were able to discriminate inactive active compounds with correct classification rate (CCR) values of 0.77 to 0.95 when evaluated for the external validation set. After the virtual screening, QSAR models were used to assist in the final selection of the compounds to be experimentally evaluated. This strategy allowed the identification of 12 compounds that were selected and acquired for in vitro assays against Leishmania (L.) infantum (MHOM / BR / 1972 / LD) in promastigote and amastigote forms, and determination of selectivity/cytotoxicity in NCTC in mammalian cells. Of the twelve compounds tested, six of them showed 50% inhibitory concentration (IC50) values raging from 3.48 to 58.94 μM and were more potent than the standard drug meglumine antimoniate, which is the drug of choice for the treatment of all forms of leishmaniasis. Three most promising compounds (LabMol-007, LabMol-009 and LabMol-012), had activity in leishmanicidal as amastigote and selectivity index promising (IC50 < 5.21 μM and selectivity index > 6.8) and were selected as new hits. We analyzed the parasite metabolic changes in the presence of known CYP51 inhibitors and new inhibitors using HR-MAS NMR 1H . We observed major changes in the energetic metabolism, amino acids catabolism, sterol biosynthesis, purine biosynthesis and thiol-redox system of the parasite. The three hit compounds identified in this work will continue in the drug development process, being necessary to carry out in vivo studies, elucidation of the mechanism of action, hit optimization, as well as the study of pharmacokinetic properties and toxicity.
Tendo em vista o quadro alarmante da leishmaniose visceral no Brasil e no mundo, especialmente devido ao crescente número de casos de resistência e aos poucos medi- camentos disponíveis, é imprescindível a busca de novas alternativas terapêuticas para esta parasitose. O sequenciamento completo do genoma das principais espécies de Leish- mania abriu grandes possibilidades no entendimento desses organismos e iniciou a era pós-genômica da descoberta de fármacos contra tripanossomatídeos. Nesse contexto, destaca-se a enzima 14 a-esterol desmetilase (CYP51) de Leishmania, que é especial- mente envolvida na biossíntese do ergosterol, principal esterol de membrana e vital para o parasito. Além disso, recentemente foi demonstrado que a inibição da CYP51 de L. donovani é essencial para o crescimento do parasito, sendo, portanto, um alvo validado para o desenvolvimento de novos fármacos leishmanicidas. O objetivo geral deste trabalho foi o desenvolvimento e a aplicação de estratégias integradas em Química Medicinal para a identificação de novas substâncias bioativas contra L. infantum, utilizando a enzima CYP51 como alvo molecular. Para isso, foram compilados, integrados e preparados os maiores conjuntos de dados disponíveis publicamente relacionados a CYP51 e a ensaios fenotípicos para Leishmania spp. Modelos de triagem virtual (VS) foram construídos, exaustivamente validados e aplicados para filtrar uma quimioteca com mais de 1 milhão de compostos comerciais. Os melhores modelos para a VS foram o ROCS (LBDD) e o farmacofórico (SBDD), com valores de área sob a curva ROC (AUC) de 0,86-0,90. O consenso entre esses dois modelos foi superior com valor de AUC de 0,93 e alta capacidade de reconhecimento de ligantes ativos no topo de 1% hits. Modelos de relação quantitativa entre estrutura e atividade (QSAR) robustos e preditivos foram gerados e validados para um conjunto de dados de compostos com atividade contra L. infantum (formas amastigota). Os modelos de QSAR foram capazes de discriminar compostos ati- vos de inativos com uma taxa de acerto (CCR) de 0,77-0,95, quando avaliados utilizando o conjunto de validação externa. Após a triagem virtual, os modelos de QSAR foram usados para auxiliar na seleção final dos compostos a avaliados experimentalmente. Essa estratégia permitiu a identificação de 12 compostos que foram selecionados e adquiridos para realização de ensaios de atividade biológica in vitro contra Leishmania (L.) infantum (MHOM/BR/1972/LD) em formas promastigotas e amastigotas, e determinação de sele- tividade/citotoxidade em células mamíferas NCTC. Dos doze compostos testados, seis deles apresentaram valores de concentração inibitória de 50% (IC50) entre 3,48-58,94 μM e foram mais potentes que o fármaco padrão antimoniato de meglumina, que é o fármaco de primeira escolha para o tratamento de todas as formas de leishmaniose. Três compostos mais (LabMol-007, LabMol-009 e LabMol-012) tiveram atividade em leishmanicida na forma amastigota e índice de seletividade bastante promissores (IC50 < 5,21 μM e índice de seletividade > 6,8) e foram selecionados como novos hits. Analisou-se as alterações metabólicas do parasito na presença inibidores conhecidos de CYP51 e dos novos inibi- dores, empregando-se RMN HR-MAS 1H. Foram observadas alterações principais nas vias de metabolismo energético, catabolismo de aminoácidos, biossíntese de esteróis, metabolismo purinas e no sistema tiol-redox do parasito. Os três hits identificados neste trabalho prosseguirão no processo de desenvolvimento de novos fármacos, sendo necessá- ria a realização de estudos in vivo, elucidação do mecanismo de ação, otimização dos hits, além do estudo de propriedades farmacocinéticas e toxicidade.

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45

Bailey, B., David Wood, Andrea Clements, Kerry Proctor-Williams, Kara Boynewicz, K. Trivette, and N. Justice. "Poly-drug Use and Other Risk Factors Among Women Receiving MAT During Pregnancy: Challenges for Research on Health and Developmental Effects in Infancy and Beyond." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/1816.

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Velez, Maria Rita Perdigão. "Epidemiology and control of canine leishmaniosis: characterization of a previously undescribed endemic area in Catalonia and CaniLeish® vaccine field trial." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/664654.

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Leishmaniosis is an important vector-borne zoonosis caused by Leishmania infantum. The disease is widespread across several continents and endemic in the Mediterranean region. The domestic dog is the main vertebrate reservoir for the parasite and control of canine leishmaniosis (CanL) is deemed to be essential for the control of human cases of the disease. Due to the heterogeneous distribution of infection in endemic areas, epidemiological surveillance should be carried out focally, including both screening of canine populations and vector detection, the two determinant factors for parasite survival and expansion. CanL control measures are usually directed at the canine reservoir through the detection and treatment of infected individuals, as well as disease prevention through insecticide treatments and/or canine immunoprophylaxis. Vaccination against CanL is relatively recent and evidence of its impact in infection control at the community level is still insufficient. This is also the case for CaniLeish® vaccine, the first CanL vaccine to be licensed in Europe, in 2011. Pre-licensing studies were performed exclusively in homogeneous populations of beagle dogs, experimentally infected or introduced in endemic areas, and very little is known regarding this vaccine’s performance in native and heterogeneous dog populations from L. infantum endemic areas. The study presented in this thesis is divided into two parts. The first consists of a CanL epidemiological study in Girona province, a previously uncharacterized region of north-eastern Spain. The results obtained confirmed the endemicity of CanL in Girona province, characterized by a high prevalence of L. infantum infection in dogs (19.5%), together with the detection of a significant proportion of asymptomatic infected individuals (93.2%). The increase of dogs’ age and lower altitude of the kennel location were identified as risk factors. The two antigens tested to assess dog exposure to Phlebotomus perniciosus (SGH and rSP03B salivary antigens) proved to be suitable, with specific antibodies showing a marked decrease during the non-transmission season, which allowed detection of recent host exposure to vectors. In addition, detected levels of antibodies against both SGH and rSP03B were associated with seropositivity to L. infantum. The second part of this thesis describes a one year field trial of CaniLeish® vaccine, performed in a native heterogeneous canine population from Girona province. These dogs were kept in their natural housing conditions throughout the study and were naturally exposed to an L. infantum transmission season. Results showed that CaniLeish® vaccine induces the production of non-specific antibodies interfering with the serological diagnosis of L. infantum infection in dogs and that this interference could have a greater impact between one and four months post-vaccination. Vaccine trial results did not confirm CaniLeish® reported efficacy in preventing active L. infantum infection or clinical disease in dogs during the first year post-vaccination. These results were supported by an apparently short-lived vaccine-induced cellular mediated immunity, assessed in this study through the quantification of gamma-interferon (IFN-γ) produced by trial dogs at one and nine months post-vaccination. The results presented in this thesis support the need for maintaining and extending epidemiological surveillance in CanL endemic areas, in order to better characterize current CanL distribution and to anticipate possible L. infantum expansion trends. Additionally, further CaniLeish® evaluation studies are needed, together with active vaccine surveillance, to definitely assess the utility of this vaccine in CanL control at the community level in L. infantum endemic areas.
La leishmaniosis es una zoonosis de transmisión vectorial que en la región mediterránea está causada por Leishmania infantum y presenta al perro como principal reservorio. Su distribución heterogénea hace que la vigilancia epidemiológica deba realizarse de manera focalizada, abarcando tanto la detección de perros infectados como de los flebotomos vectores. Las medidas de control de la leishmaniosis canina (LCan) incluyen la vacunación de perros. En Europa, la primera vacuna para la LCan (CaniLeish®) se autorizó en 2011 y los estudios previos a la licencia se realizaron exclusivamente en poblaciones homogéneas de perros beagle, infectados experimentalmente o introducidos en áreas endémicas. La primera parte de la tesis incluye un estudio epidemiológico de la LCan en la provincia de Girona, previamente sin caracterizar. Los resultados obtenidos mostraron una alta prevalencia de infección por L. infantum (19,5%) y una proporción significativa de individuos infectados asintomáticos (93,2%). Se identificaron como factores de riesgo el aumento de la edad de los perros y la menor altitud de la ubicación de las perreras. El estudio de la exposición de los perros a los flebotomos a través del análisis de los antígenos salivales de Phlebotomus perniciosus (SGH y rSP03B) mostró ser útil. Los niveles de anticuerpos detectados mostraron una marcada disminución durante la temporada de no transmisión, lo que permitiría la detección de la exposición reciente a los vectores, y una asociación significativa con la seropositividad frente a L. infantum. La segunda parte describe un ensayo de campo de un año de CaniLeish®, realizado en una población canina heterogénea natural de Girona. Los perros se mantuvieron en condiciones habituales de alojamiento y estuvieron naturalmente expuestos a una temporada de transmisión. La vacuna indujo la producción de anticuerpos no específicos que interferirían en el diagnóstico serológico de la infección por L. infantum, con un impacto mayor entre uno y cuatro meses después de la vacunación. Los resultados no confirmaron la eficacia de CaniLeish® en la prevención de la infección activa por L. infantum o la enfermedad clínica en perros durante el primer año post-vacunación. Estos resultados fueron respaldados por una inmunidad mediada por células inducida por la vacuna aparentemente de corta duración, evaluada a través de la cuantificación del interferón gamma (IFN-γ).

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Richter, Bárbara Rocha. "Hiperatividade ou indisciplina : o TDAH e a patologização do comportamento desviante na escola." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/55071.

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O Transtorno do Déficit de Atenção e Hiperatividade (TDAH) configura-se, atualmente, como um dos transtornos cada vez mais diagnosticados em indivíduos de idade escolar. Ao invés de tomar o TDAH como um fato científico isolado, proponho, através deste estudo, pensá-lo como um fenômeno vinculado à cultura. Para tanto, valho-me do referencial teórico-metodológico dos Estudos Culturais e pós-estruturalistas. Busco problematizar as estratégias voltadas ao controle dos corpos hiperativos na escola, pensando a emergência do TDAH no solo da cultura somática, bem como sua relação com o processo a que se tem chamado de medicalização do ensino, fenômeno que vem acompanhado do uso de psicofármacos como solução para problemas de comportamento em sala de aula. Analiso exemplares da revista Nova Escola, no período de 1986 (ano inicial de sua publicação) a 2011, operando com as matérias cujo título ou o conteúdo versassem sobre hiperatividade, desatenção e/ou indisciplina. Observo o modo como o discurso neurocientífico atravessa as noções de sujeito e de que maneira esse atravessamento implica em práticas no âmbito da escola. Esta discussão permite observar que os processos de biologização, patologização e medicalização constituem fenômenos interligados e fortemente articulados ao TDAH na contemporaneidade. Assim, o diagnóstico de TDAH e o uso de psicofármacos se mostraram, na análise deste trabalho, como uma nova forma de controle e disciplinamento do corpo infantil/escolar. Aponto para a necessidade de um questionamento acerca da transferência de problemas de ordem escolar para a esfera médica.
The Attention Deficit and Hyperactivity Disorder (ADHD) is currently one of the increasingly diagnosed disorders in individuals of school age. Instead of taking ADHD as an isolated scientific fact, I propose, through this study, think of it as a phenomenon linked to the culture. For this, I use the theoretical and methodological referential of Cultural Studies and poststructuralists. I attempt to analyze the strategies aimed at controlling hyperactivities bodies in the school, thinking about the emergence of ADHD in the context of somatic culture, and its relation to the process that has been called medicalization of education. This phenomenon has accompanied the use of psychotropic drugs as a solution to behavior problems in the classroom. I analyze copies of the magazine Nova Escola for the period 1986 (initial year of its publication) to 2011, operating with reports of hyperactivity, inattention and indiscipline. I regard how neuroscientific discourse through the concepts of subject and how this involves practices within the school. This discussion allows us to note that biologization, pathologizing and medicalization are interconnected process and strongly articulated with TDAH in contemporary. Thus, the diagnosis of ADHD and the use of psychotropic drugs constitute a new form of control and discipline of the infant’s body. I point to the need to question about the transfer of problems in educational to the medical area.

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Silva, Carlos José Nieto. "Consumo de drogas en tres etapas de la vida de habitantes de calle de Bogotá : predictores de consumo y comparación con una muestra de población infantil y adolescente de Brasil." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2011. http://hdl.handle.net/10183/37297.

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Os objetivos desta pesquisa foram identificar os principais preditores do nível de consumo de drogas no ciclo vital de moradores de rua da cidade de Bogotá (Estudo I), assim como as possíveis diferenças de consumo entre crianças e adolescentes em situação de rua de Bogotá e de algumas cidades do Brasil (Estudo II). Para cumprir estes objetivos, foram analisas as bases de dados do V Censo de Moradores de Rua de Bogotá, de 2007, assim como os dados do Levantamento Nacional Sobre Uso de Drogas entre Meninos, Meninas e Adolescentes em Situação de Rua do Brasil, realizado no ano de 2003. No Estudo I, foram criados três grupos, segundo três etapas da vida: infância-adolescência, adultez e velhice, usando a base de dados de Bogotá. A amostra do grupo de crianças e adolescentes foi de 486 participantes, 72% homens, com idades entre 8 e 17 anos (M = 14.76; DP = 2.24). A amostra de adultos foi de 6.275 participantes, 88% homens, com idades entre 18 e 59 anos (M = 35.66; DP = 10.78). A amostra de idosos foi de 228 participantes, 92% homens, com idades entre 60 e 92 anos (M = 65.28; DP = 5.39). Foram realizadas análises de regressão múltipla hierárquica para identificar os preditores do nível de consumo de drogas entre 16 variáveis, que incluíam aspectos sociodemográficos, de saúde mental e de vivência na rua. As variáveis preditoras do nível de consumo, incluídas nos modelos da análise de regressão, variaram entre as três etapas da vida. Entretanto, o nível de violência e delinquência cometido enquanto habitante de rua, e o consumo de cigarro, foram as variáveis que tiveram maior capacidade de predição do nível de consumo de drogas dos habitantes de rua, ao longo das três etapas do ciclo vital desta população. Para o Estudo II, foram selecionados dois grupos de meninos, meninas e adolescentes em situação de rua, sendo um grupo de Bogotá e o outro oriundo de 13 cidades capitais do Brasil. Cada grupo contou com 392 participantes (n = 784), com idades entre 10 e 18 anos, 79% homens, sendo que 57% dormiam principalmente na rua. Os casos foram sorteados aleatoriamente das bases de dados disponíveis, pareando a amostra por sexo, idade e local de dormida. Os resultados das comparações demonstraram que a amostra do Brasil teve um maior percentual médio da quantidade de tipos de drogas consumidas durante o último ano, sendo que o consumo de inalantes, de álcool e de cigarro foram superiores quando comparado com Bogotá. Em contrapartida, a amostra de Bogotá teve médias superiores na frequência de consumo de cocaína e seus derivados, e foi vítima de um maior nível de violência, incluindo a violência sexual. Estes resultados foram discutidos especialmente no que se refere à relação entre gênero, violência, delinqüência, contexto social e temporal das amostras, e consumo de drogas.
The purpose of this research was to identify predictors of drug use in the life spam of homeless in Bogotá (Study I) and to compare their consumption, in the segment of childhood and adolescence, with a similar sample of major capital cities of Brazil (Study II). It was analyzed the databases of the Fifth Census of Homeless in Bogota, held in year 2007, as well as the National Survey on Drug Use Among Street Children and Adolescents of Brazil, held in year 2003, to accomplish this goal. For the Study I sample was 6989 participants of the census of homeless in Bogota, 6989 (M = 35.23, SD = 13.05, 87% male). The predictors of drug use varied among the three stages of life, in the regression analysis. However, the level of violence and crime committed as a homeless, and cigarette use level were the variables that had greater predictability of level of drug use in street people of all ages in Bogota. For Study II, two groups of streets children and adolescents from Bogota and 13 capital cities of Brazil (n = 784), aged between 10 and 18, who were randomly selected from the data bases available, matching the sample by sex, age and place where they sleep, were selected. The comparison results indicated that the sample of Brazil had a higher average percentage of number of types of drugs used in the past year, and in this sample the use of inhalants, alcohol and smoking was higher. While the sample of Bogota had a higher average frequency of cocaine use and its derivatives, and they were victims of more violence, including sexual violence. These results were discussed, especially with regard to the relationship among sex, violence, crime and drug use.
Los objetivos de esta investigación fueron identificar los principales predictores de nivel de consumo de drogas en el siclo vital de habitantes de calle de Bogotá (Estudio I), así como las posibles diferencias de consumo entre niños y adolescentes en situación de calle de Bogotá y algunas ciudades de Brasil (Estudio II). Para llevar a cabo estos objetivos se analizó las bases de datos del V Censo de Habitantes de Calle de Bogotá de 2007, así como la del Levantamiento Nacional Sobre Uso de Drogas entre Niños, Niñas y Adolescentes en Situación de Calle de Brasil, realizado en el año de 2003. En el Estudio I se crearon tres grupos según tres etapas de la vida: Infancia-adolescencia, adultez y vejez, usando la base de datos de Bogotá. La muestra del grupo de niños y adolescentes fue 486 participantes, 72% hombres, con edades entre 8 – 17 años (M = 14.76, DS = 2.24). La muestra de adultos fue de 6275 participantes, 88% hombres, con edades entre 18 – 59 años, (M = 35.66, DS = 10.78). Y la de ancianos de 228 participantes, 92% hombres, con edades entre 60 – 92 años, (M = 65.28, DS = 5.39). Se realizaron Análisis de Regresión Lineal Múltiple Jerárquica para identificar predictores de nivel de consumo de drogas dentro de 16 variables que incluían aspectos sociodemográficas, de salud mental y de habitabilidad en calle. Las variables predictoras del nivel de consumo, incluidas en los modelos arrojados por los análisis de regresión, variaron entre las tres etapas de la vida. Sin embargo, el nivel de violencia y delincuencia cometida como habitante de calle, y el nivel de consumo de cigarrillo, fueron las variables que tuvieron mayor capacidad de predicción de niveles de consumo de drogas en habitantes de la calle en las tres etapas de esta población. Para el Estudio II, se seleccionaron dos grupos de niños, niñas y adolescentes en situación de calle de Bogotá y 13 de las ciudades capitales de Brasil. Cada grupo contó con 392 participantes (n = 784), con edades entre 10 y 18 años, 79% hombres, siendo que 57% dormían principalmente en la calle. Los casos fueron elegidos aleatoriamente de las bases de datos disponibles, pareando la muestra por sexo, edad y lugar donde duermen. Los resultados de las comparaciones señalaron que la muestra de Brasil tuvo un mayor porcentaje promedio de cantidad de tipos de drogas consumidas durante el último año, y allí el consumo de inhalantes, de alcohol y de cigarrillo fue superior. Mientras que la muestra de Bogotá tuvo promedios superiores en la frecuencia de consumo de cocaína y sus derivados, y fue víctima de un mayor nivel de violencia, incluida la violencia sexual. Estos resultados fueron discutidos, especialmente lo referente a la relación entre género, violencia, delincuencia y consumo de drogas.

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Gomes, Rafael Kmiliauskis Santos. "Impacto dos medicamentos imunobiológicos e da doença coronária na evolução de pacientes com artrite reumatoide: uma análise de custo-efetividade." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5137/tde-24082017-080027/.

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Introdução: Estudos epidemiológicos têm estabelecido que a artrite reumatoide está associada com um aumento de doença cardiovascular. A avaliação de anti-TNF sobre a redução do risco de infarto agudo do miocárdio e óbito por causa cardiovascular tem demonstrado resultados promissores. A avaliação econômica para esses desfechos ainda não está estabelecida. Objetivo: Realizar uma análise de custo efetividade de anti-TNF versus Dmards para evitar um caso novo de morbidade e óbito cardiovascular na artrite reumatoide. Método: Foi realizada uma análise de custo efetividade por meio do modelo de Markov, ciclo de transição de 6 meses e horizonte temporal de 30 anos sob perspectiva do sistema público de saúde do Brasil mensurado pela razão de custo efetividade incremental. Custo em Reais no ano de 2015 e efetividade em evitar um caso novo de doença coronariana isquêmica aguda e óbito cardiovascular. Resultados: O custo médio em 30 anos de Dmards e anti-TNF foi de R$ 14.291.105,28 e R$ 96.151.873,86, respectivamente. A efetividade incremental para doença arterial coronariana foi de 2,69 e consequente razão incremental de custo efetividade de R$ 30.527.502,27, enquanto para óbito cardiovascular a efetividade incremental foi de 1,33 casos evitados e uma razão incremental de custo efetividade de R$ 61.634.231,69. A análise univariada identificou que o parâmetro de maior impacto na razão incremental de custo efetividade de ambos os desfechos foi o medicamento anti-TNF. A análise de sensibilidade estabeleceu que, para atingir o valor de disposição a pagar por semestre para evitar um infarto agudo do miocárdio, o custo médio do anti-TNF deveria ser de R$ 1.337,47 ou diferença de incidência entre as estratégias de 0,032. Ainda, para evitar um óbito cardiovascular, o custo médio deveria ser de R$ 954,22 ou diferença de incidência de 0,071. Todas as análises realizadas estabeleceram uma relação desfavorável da estratégia do tratamento medicamentoso com anti-TNF. Conclusão: Os achados da análise de custo efetividade entre pacientes com artrite reumatoide para desfecho cardiovascular quando comparada a estratégia de tratamento medicamentoso de anti-TNF em relação à estratégia dominante com Dmards após os 6 primeiros meses de exposição aos medicamentos apontaram para uma relação desfavorável, ultrapassando o valor de disposição a pagar recomendado pelo Ministério da Saúde do Brasil no ano de 2015. Descritores: artrite reumatoide; doenças cardiovasculares; infarto do miocárdio; óbito; avaliação de custo-efetividade; anti fator de necrose tumoral; drogas anti-reumáticas modificadoras de doença.
Introduction: Epidemiological studies have established that rheumatoid arthritis is associated with an increase in cardiovascular disease. The evaluation of anti-TNF on the reduction of the risk of acute myocardial infarction and death due to cardiovascular causes has shown promising results. The economic evaluation for these outcomes is not yet established. Objective: To perform a cost-effectiveness analysis of anti-TNF versus Dmards to avoid a new case of cardiovascular morbidity and death in rheumatoid arthritis. Method: A cost effectiveness analysis was performed using the Markov model, a 6-month transition cycle and a 30-year time horizon under the perspective of the Brazilian public health system measured by the incremental cost-effectiveness ratio. Cost in Reais in the year 2015 and effectiveness in avoiding a new case of acute ischemic coronary disease and cardiovascular death. Results: The average cost in 30 years of Dmards and anti-TNF was R$ 14,291,105.28 and R$ 96,151,873.86, respectively. The incremental effectiveness for coronary artery disease was 2.69 and a consequent incremental cost-effectiveness ratio of R$ 30,527,502.27, while for cardiovascular death, incremental effectiveness was 1.33 cases avoided and an incremental cost-effectiveness ratio of R$ 61,634,231.69. The univariate analysis identified that the parameter of greatest impact in the incremental cost-effectiveness ratio of both outcomes was the anti-TNF drug. The sensitivity analysis established that the average cost of anti-TNF should be R$ 1,337.47 or incidence difference between strategies of 0.032 in order to reach the amount of willingness to pay per semester to avoid an acute myocardial infarction. Also, to avoid a cardiovascular death, the average cost should be R$ 954.22 or incidence difference of 0.071. All the analyzes carried out established an unfavorable relationship of the drug treatment strategy with anti-TNF. Conclusions: The findings of the cost-effectiveness economic analysis among individuals with rheumatoid arthritis for cardiovascular outcome when compared to the strategy of anti-TNF drug treatment compared to the dominant strategy with Dmards after the first 6 months of drug exposure pointed to an unfavorable relationship, surpassing the amount of willingness to pay recommended by the Ministry of Health of Brazil in the year 2015.

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Baltieri, Danilo Antonio. ""Consumo de álcool e outras drogas e impulsividade sexual entre agressores sexuais"." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5142/tde-22032006-221450/.

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INTRODUÇÃO: A violência sexual é um importante problema de saúde pública. Em São Paulo, cerca de 5% dos apenados estão cumprindo pena por crimes sexuais violentos. No Brasil e em outros países, muitos agressores sexuais retornarão à sociedade sem quaisquer intervenções psicossociais para prevenir a reincidência criminal. O objetivo deste estudo foi avaliar o consumo de álcool e de outras drogas e a impulsividade sexual entre agressores sexuais. MÉTODOS: Trata-se de estudo observacional, retrospectivo e seccional realizado na Penitenciária de Sorocaba São Paulo. Entre julho de 2004 e setembro de 2005, todos os 218 sentenciados apenas por crimes sexuais violentos foram entrevistados, avaliando o consumo de álcool e de outras drogas, impulsividade, dependência de sexo e risco de reincidência criminal, além dos seus prontuários jurídicos revisados. 20 (9,17%) sentenciados foram excluídos da amostra. Os agressores sexuais foram divididos em três grupos: molestadores de crianças (n = 101), agressores sexuais de adolescentes (n = 56) e agressores sexuais de adultos (n = 41). Além disso, os apenados foram também divididos em outros três grupos, de acordo com o número de vítimas envolvidas: agressores sexuais de uma vítima (n = 149), agressores sexuais de duas vítimas (n = 25) e agressores sexuais de três ou mais vítimas (n = 24). RESULTADOS: 1) Agressores sexuais de adultos foram mais jovens do que os outros dois grupos de agressores sexuais (p < 0,01); 2) Agressores sexuais de adultos mostraram mais problemas com o uso de drogas do que os outros dois grupos comparados (p < 0,01); 3) Molestadores de crianças mostraram significativamente maior gravidade de dependência de álcool do que os outros dois grupos (p < 0,01); 4) Molestadores de crianças do sexo masculino mostraram maior gravidade de dependência de álcool do que os molestadores de crianças do sexo feminino (p < 0,01); 5) Agressores sexuais seriais apresentaram significativamente maior nível de impulsividade do que os agressores não seriais (p < 0,01); 6) Agressores sexuais seriais registraram mais freqüentemente história de abuso sexual na infância do que os agressores sexuais de uma vítima (p < 0,01). CONCLUSÕES: O consumo de substâncias psicoativas pode ser um dos fatores de distinção entre molestadores de crianças e agressores sexuais de adultos. História de abuso sexual e altos níveis de impulsividade podem estar associados com a repetição do comportamento sexualmente agressivo.
INTRODUCTION: Sexual violence is an important public health problem. In São Paulo, about 5% of male prison inmates are serving a sentence for a serious sexual offense. In Brazil and other countries, many sexual offenders will return home without any psychosocial interventions to prevent recidivism. The aim of this study was to evaluate the role of alcohol and drug consumption and the sexual impulsivity level among sexual offenders. METHODS: It was an observational, retrospective and cross-sectional study carried out inside the Penitentiary of Sorocaba São Paulo. From July 2004 to September 2005, all 218 convicts sentenced only for sexual crimes were evaluated with reference to alcohol and drug use, impulsivity, sexual addiction, recidivism risk and their juridical reports were reviewed. 20 (9.17%) recruited convicts were excluded from the sample. The sexual offenders were divided in three groups, such as children molesters (n= 101), sexual aggressors against adolescents (n = 56) and sexual offenders against adults (n = 41). Moreover, the sexual offenders were also divided in three groups with reference to the number of involved victims, such as sexual aggressors against one victim (n = 149), sexual offenders against two victims (n = 25) and sexual offenders against three or more victims (n = 24). RESULTS: 1) Sexual offenders against adults were found to be significantly younger than children molesters and sexual offenders against adolescents (p < 0.01); 2) Sexual offenders against adults had more difficulties with drug use than the comparison groups (p < 0.01); 3) Children molesters showed significantly higher severity of alcohol dependence than the comparison groups (p < 0.01); 4) Children molesters against boys showed significantly higher severity of alcohol dependence than children molesters against girls (p < 0.01); 5) Serial sexual offenders had significantly higher impulsivity level than nonserial sexual offenders (p < 0.01); 6) Serial sexual offenders reported significantly more personal history of being sexually abused than nonserial sexual offenders (p < 0.01). CONCLUSIONS: Substance use may be one of the distinguishing factors between offenders who target children and those who target adults. History of sexual abuse and high impulsivity levels may be associated with the repetition of sexual aggression.

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Dissertations / Theses on the topic 'Drugs and infants'

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