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Pharmacokinetic and Pharmacodynamic Modeling of Antibiotics and Bacterial Drug ResistanceSyed Mohamed, Ami Fazlin January 2013 (has links)
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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The infant feeding experiences and decision-making influences of Aboriginal women in SaskatoonWagner, Maya 14 September 2007
Breastfeeding is the optimal form of infant feeding. It appears to protect children from certain childhood diseases that are over represented in the Aboriginal population. Although breastfeeding rates in the general Canadian population have increased over the past two decades, they remain lower than recommended. Rates in the Canadian Aboriginal population are even lower. Breastfeeding literature among Aboriginals is largely demographic and statistical in nature and focuses primarily on First Nations women living on reserves. The purpose of this study was to investigate the factors influencing the infant feeding decisions of Aboriginal women living in Saskatoon. Data were collected using qualitative methods, including face-to-face interviews and prolonged observation. Between October 2003 and May 2004, interviews were conducted with a total of eight participants recruited from the Food for Thought program in Saskatoon. A semi-structured prenatal interview was followed by two unstructured, in-depth interviews at approximately one month postpartum. The researcher's participation in two weekly Food for Thought sessions over the same time period allowed for prolonged observation. Observations were recorded using field notes and interviews were tape-recorded and transcribed verbatim. Observation and interview data from each participant were analyzed separately for dominant themes and then integrated to establish collective influencing factors. Results indicated influencing factors are numerous and varied in nature. Contextual (sociocultural and environmental), attitudinal, cognitive (knowledge, information and beliefs), experiential (previous infant feeding experiences), and psychological influences were revealed. The principle implication of this study for those involved with the protection, support, and promotion of breastfeeding in this population is that there are many factors capable of influencing feeding decisions. Feeding decisions are not static; they are dynamic and result from the complex interplay between influencing factors. The importance or significance of any single factor is a reflection of the circumstances surrounding the particular feeding decision.
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The infant feeding experiences and decision-making influences of Aboriginal women in SaskatoonWagner, Maya 14 September 2007 (has links)
Breastfeeding is the optimal form of infant feeding. It appears to protect children from certain childhood diseases that are over represented in the Aboriginal population. Although breastfeeding rates in the general Canadian population have increased over the past two decades, they remain lower than recommended. Rates in the Canadian Aboriginal population are even lower. Breastfeeding literature among Aboriginals is largely demographic and statistical in nature and focuses primarily on First Nations women living on reserves. The purpose of this study was to investigate the factors influencing the infant feeding decisions of Aboriginal women living in Saskatoon. Data were collected using qualitative methods, including face-to-face interviews and prolonged observation. Between October 2003 and May 2004, interviews were conducted with a total of eight participants recruited from the Food for Thought program in Saskatoon. A semi-structured prenatal interview was followed by two unstructured, in-depth interviews at approximately one month postpartum. The researcher's participation in two weekly Food for Thought sessions over the same time period allowed for prolonged observation. Observations were recorded using field notes and interviews were tape-recorded and transcribed verbatim. Observation and interview data from each participant were analyzed separately for dominant themes and then integrated to establish collective influencing factors. Results indicated influencing factors are numerous and varied in nature. Contextual (sociocultural and environmental), attitudinal, cognitive (knowledge, information and beliefs), experiential (previous infant feeding experiences), and psychological influences were revealed. The principle implication of this study for those involved with the protection, support, and promotion of breastfeeding in this population is that there are many factors capable of influencing feeding decisions. Feeding decisions are not static; they are dynamic and result from the complex interplay between influencing factors. The importance or significance of any single factor is a reflection of the circumstances surrounding the particular feeding decision.
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Risk factors associated with compromised birth outcomes among Mexican origin population in El Paso, Texas: a postpartum hospital studyGonzález Ramírez, Raúl S. 28 August 2008 (has links)
Not available / text
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The interaction between human leucocyte antigen-G and natural killer cells at the placental interface in HIV-1 infected pregnant women and the significance, if any, to in utero transmission.January 2007 (has links)
This study was undertaken to investigate the relationship between Natural Killer cells and HLA-G at the placental barrier in HIV-I infected pregnant women and to establish the significance, if any, to in utero infection. Fifty-five HIV -I infected pregnant women were recruited into the study after consent was obtained. Blood samples were collected from both mothers and babies for viral loads and CD4+ cell counts. Placental samples were obtained from pregnancies at delivery and examined by immunoperoxidase immunohistochemistry methods using monoclonal antibodies to p24 antigens and Natural Killer (CD56+) cells. HLA-G expression was quantified using real-time polymerase chain reaction. Analysis of viral loads and CD4+ cell counts were undertaken in categories. No significant association was observed between the viral load of mothers and their CD4+ cell counts. Eighteen percent of the women in this study population had 5 log viral loads with a transmission rate of 0.27(95% Cl, 0.15 - O. 39). Maternal viraemia was significantly associated with transmission of infection to babies (p = 0.047). The odds ratio indicated that for every 1 log increase in maternal viral load the babies were 3.1 times more likely to acquire the infection (Exp (B) = 3.137 (95%CI, 1.015-9.696). Furthermore, the study found that a higher number of female babies were infected than males. Although not statistically significant the odds ratio indicated that female babies were 3.1 times more likely to become infected than males (Exp (B) = 3.110 (95%CI, 0.819-11.808). We report here the results of immunohistochemistry for p24 antigens and NK (CD56+) cells and compare them to the immunological responses of both mothers and babies at birth. HIV-1 antigens were detected in 94.5% of all placentas by immunohistochemistry. Infiltration of CD56+ was found in 98% of placental tissue. The analysis revealed that the presence of p24 antigens in placental tissue was not influenced by maternal viral load or CD4+ cell counts. Lower median NK cell values were observed in placentas of mothers with infected babies as compared with the uninfected cluster. Although not statistically significant, the risk of vertical transmission was increased 3.4 times more in placentas which had lower NK cell values. According to the odds ratio, babies CD4+ counts were affected by every 1 log increase in mother's viral load. Overall, maternal viral load emerged as a strong predictor for risk of infection from infected mothers to their infants. Our analysis indicated that female babies were 3.7 times more likely to acquire the infection than males. Using data obtained from real-time PCR we investigated the relationship between maternal viral load and the quantity of HLA-G expression (p = 0.045; 95%CI 1.029- 11.499). Logistic regression models revealed that mother's viral load was the strongest risk factor for vertical transmission. No statistically significant correlation was noted with HLA-G and viral transmission. However, the odds ratio indicated that the risk of infection increased by 1.3 with every 1 fold increase in HLA-G expression. An analysis of mother-to-child transmission rates by gender revealed that the odds ratio for transmission was 3.4 times more in female babies than in males. We then investigated the relationship between maternal viraemia and HLA-G expression. A positive correlation between maternal viral load and placental HLA-G was observed (p = 0.038). When gender susceptibility to HLA-G expression was explored a statistically significant association was observed in placental tissue of mothers with infected and uninfected male babies and HLA-G expression (p = 0.013). To conclude, the analysis found that HLA-G was up regulated 3.95 times more in placental tissue of mothers with infected babies than in mothers with uninfected babies. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2007.
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An exploration of emerging problems for infant feeding options : some obstacles for the rapid expansion of the HIV mother-to-child transmission prevention programme : the KwaZulu-Natal experience.Smith, Elaine. January 2003 (has links)
No abstract available. / Thesis (M.A.)-University of Natal, Durban, 2003.
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The impact of pneumonia in human immunodeficiency virus (HIV-1) infected pregnant women on perinatal and early infant mortality.January 2007 (has links)
Background: Although the prevalence of pneumonia in pregnancy is reported to be less than 1%, the pregnant state and risk factors associated with the development of pneumonia adversely influence the outcome of pregnancy. KwaZulu-Natal is at the epicenter of the dual epidemics of tuberculosis and HIV-1 and the impact of these diseases occurring concurrently in pregnant women at King Edward VIII hospital (KEH), South Africa have been described previously. The impact of antenatal pneumonia in HIV-1 infected and uninfected women however has not been described in the study population and was investigated. Methods: Pregnant women with clinical and radiological evidence of pneumonia were recruited from the antenatal clinic and labour ward at KEH. The study was conducted prospectively between January and December 2000. The clinical profile of these women and the causative organisms were determined. In addition the impact of HIV-1 infection, maternal immunosuppression and maternal pneumonia on obstetric and perinatal outcomes were evaluated. Mothers diagnosed with tuberculosis and multi drug resistant tuberculosis were hospitalised at King George V hospital until delivery. Results: Twenty nine women were diagnosed with antenatal pneumonia (study arm) with Mycobacterium tuberculosis the only causative organism isolated. A control arm of 112 pregnant women was also studied. Maternal and perinatal mortality was restricted to the study arm with a maternal mortality ratio of 99 per 100 000 live births and a perinatal mortality rate of 240 per 1000 births. Pneumonia was significantly associated with a negative overall obstetric outcome in the presence of HIV- l infection, antenatal care, anaemia and second trimester booking status. In addition, the presence of pneumonia was significantly associated with maternal mortality. There was a highly significant association between exposure to pneumonia and poor neonatal outcome. Maternal pneumonia, maternal HIV infection and the presence of medical and obstetric conditions were significantly associated with low birth weight and neonatal pneumonia. Further, maternal pneumonia (p <0.001) and concurrent HIV infection (p=0.002) was significantly associated with neonatal death. Conclusion: The presence of pneumonia in the antenatal period impacts negatively on maternal and neonatal morbidity and mortality. Health care providers must maintain a high degree of suspicion when managing a pregnant woman with unresolving upper respiratory tract symptoms and refer timeously for further investigation. Pneumonia and in particular pulmonary tuberculosis associated with HIV co- infection in pregnancy is a threat to mother and baby. Therefore in areas endemic for TB and HIV infection, it may be prudent to screen HIV positive pregnant women for symptoms suggestive of pneumonia and thereby identify women requiring further investigations such as sputummicroscopy and cultures, and a screening chest radiograph. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2007.
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The effectiveness of three treatment regimens used in the management of neonatal abstinence syndromeKhoo, Khooi Tin Unknown Date (has links) (PDF)
This study proposed a multifactorial model of development to understand the development of infants during their first 12 months of life who had been born to chemically dependent women. The impact of maternal chemical dependency on pregnancy outcome, factors associated with severity of neonatal abstinence syndrome and effectiveness of three treatments used in the management of neonatal abstinence syndrome was studied in 271 mother-infant pairs, who were managed by the Chemical Dependency Unit, Royal Women’s Hospital, Melbourne between April 1991 and May 1994. / The chemically dependent mothers and their infants were grouped on the basis of their primary drug of abuse: viz methadone, heroin, non-opioid and codeine groups. Fifty two infants born to drug-free mothers were recruited from a routine antenatal clinic of the same hospital to serve as a control group. The controls were matched for maternal age, marital status, race socioeconomic status, educational level, alcohol and tobacco consumption. / Patterns of maternal drug use were determined by reports from methadone treatment programs, drug rehabilitation centres, medical records, personal interviews and urine toxicologic assays performed on mothers during pregnancy and on their infants during the first 48 hours of life. Urine was assayed for metabolites of methadone, amphetamines, barbiturates, cocaine, opiates, cannabis and benzodiazepines. / There were 180 heroin-dependent, one morphine-dependent and one pethidine-dependent pregnant women enrolled in methadone maintenance programs. The methadone group consisted of these 182 methadone-maintained women and their offspring. Thirty five heroin-dependent women and their offspring formed the heroin group. The non-opioid group consisted of 46 chemically dependent women who used multiple drugs but not opioid drugs during their pregnancy and their offspring. There were eight mother-infant pairs in the codeine group. The mothers in this group primarily abused medication containing codeine in pregnancy. (For complete abstract open document)
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Risk factors, rehospitalizations, and RSVWalker, Holly N. January 2008 (has links)
Thesis (M.A.)--Northern Kentucky University, 2008. / Made available through ProQuest. Publication number: AAT 1454478. ProQuest document ID: 1580779071. Includes bibliographical references (p. 25-27)
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A good start in life revisiting racial and ethnic disparities in health outcomes at and after birth /Ma, Sai. January 2007 (has links) (PDF)
Thesis (Ph.D.)--Pardee Rand Graduate School, 2007. / Title from title screen (viewed on June 13, 2008). Includes bibliographical references.
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