Dissertations / Theses on the topic 'Pelvic inflammatory disease'

In 1996, a RCOG Study Group reporting on the prevention of pelvic infection highlighted the considerable role C. trachomatis played in female reproductive morbidity and the potential advantages of DNA based assays.  A national screening programme was suggested, as Sweden and the USA had demonstrated that screening women could decrease prevalence and pelvic inflammatory disease rates. In the UK, out with genito-urinary medicine clinics, awareness of the infection and screening was virtually non-existent.  Women attending obstetric and gynaecology-affiliated clinics were at increased risk of ascending infection compared to the general public and ideally placed for opportunistic screening.  However, patients were TESTED only if symptomatic, by specimens taken from the endocervix for culture or antigen detection assay.  It was from this background that the studies commenced.  The thesis comprises of: -  A questionnaire survey assessing sexually active women’s knowledge of C. trachomatis infection and perceived acceptability of different methods and settings for screening.  Women attending induced abortion and family planning clinics in Aberdeen and Leeds were recruited. -  A prevalence study, aiming to identify who should undergo screening.  Sexually active women attending six different clinical settings in Aberdeen’s Obstetrics & Gynaecology department were screened for Chlamydia. -  A study assessing test performance and acceptability of four different screening approaches (enzyme immunoassay of endocervical specimens and ligase chain reaction assay of endocervical, clinician-collected vulva!, and urine specimens) to opportunistically screen pregnant and non-pregnant women, under 25 years of age. -  A study evaluating patient-collected vulval swabs, as an alternative to non-invasive screening by urine.  Women under 25 years of age attending a family planning clinic were opportunistically screened and test performance and acceptability evaluated. -  A study determining whether the measurement of chlamydial IgG antibodies alone or in combination with medical history and/or transvaginal ultrasound can predict tubal infertility in subfertile women.

Estimates of the cost-effectiveness of chlamydia control interventions are highly sensitive to the risk of progression from genital chlamydia infection to pelvic inflammatory disease (PID). There is no consensus for the risk of PID following asymptomatic chlamydia infections detected through population-based testing. The aim of this thesis is to generate improved estimates of this risk of PID that can be used to parameterise mathematical models and inform chlamydia control policy. We have determined the risk of PID following a positive chlamydia test in three cohorts: a small historic prospective clinical cohort of sex workers (Praed Street Project (PSP)); a large population-based retrospective cohort from Manitoba, Canada established for this research; and a large nationally representative retrospective cohort from Denmark. The risk of PID was higher in women with a positive chlamydia test compared to women who tested negative (PSP: adjusted hazard ratio (AHR) 2.03 (95%CI 0.75-5.49); Manitoba: 1.55 (95%CI 1.43-1.70); Denmark: 1.42 (95%CI 1.32-1.53)). There was heterogeneity in this risk: 13-23% higher following a repeat infection; up to four-fold higher in younger women (Manitoba: AHR 4.55 (95%CI 3.59-5.78) in 12-15 compared to 30-40 years); two-fold higher following previous gonorrhoea (PSP: 2.28 (95%CI 1.14-4.56)). The increased risk following a positive test lasted considerably longer than the likely duration of infection and fewer than 10% of PID diagnoses within 12 months of a test could be attributed to a positive result. This suggests that there are other important causes of PID. Individual-based risks of progression that capture this heterogeneity may improve the accuracy of estimates from mathematical models and therefore their utility to policy makers. Further research is needed to fully characterise the aetiology of PID to inform the design of chlamydia control interventions. In the meantime, interventions should focus on young women and those at risk of repeat chlamydia infection.

Infection by Chlamydia trachomatis is the leading cause of tubal disease and accounts for a significant proportion of the physical, psychosocial and economic burden of infertility. As it is frequently asymptomatic and opportunities for early treatment are missed, repeated/chronic infection leads to permanent/irreversible inflammation- induced tubal damage, which may extend as far as the ovary. However, not all infected women develop tubal pathology, possibly due to inherent host-specific and environment-induced differences in immune response. This study investigated the impact of putative cytokine-based gene and protein-mediated influences governing the host immune response to C. trachomatis infection and its effects on tubal pathology and ovarian function. The study population comprised 367 women whose infection status was determined serologically. Genetic predisposition to tubal disease was assessed by profiling single nucleotide polymorphism allelic variants in nine cytokines. Ovarian follicular fluid and circulatory cytokine profiles were determined by fluid-phase multiplex immunoassay, while serum antl-Mullerlan hormone levels were measured by enzyme-linked immunosorbent assay. No genetic or circulatory markers of susceptibility to tubal pathology were identified. Furthermore, tubal disease had no significant impact on ovarian function (based on ovarian reserve and follicular cytokine levels). The failure to identify genetic susceptibility markers of tubal disease may reflect the fact that the disease is under polygenic influence with superimposed environmental predisposing factors. Together with the fact that local inflammatory processes may not be reflected systemically, putative changes in cytokine profile between initial infection and the study period could explain why no serum biomarkers of tubal disease could be identified. Finally, the observation that tubal disease had no measurable effect on ovarian pathophysiology is likely to be due either to the small number of women with severe disease recruited to the study or due to other confounding factors eliminating the contribution of the infective inflammatory responses. Further investigation is thus warranted.

Pelvic Inflammatory Disease (PID) is one of the most common causes of morbidity in women. PID is a polymicrobial infection of the female reproductive tract, and is associated with pelvic pain, abnormal uterine bleeding, and tubal damage that can lead to ectopic pregnancies and infertility. It is curable but the effects of PID can be permanent if not properly diagnosed and treated. PID presents as a spectrum of disease and is often missed at early stages; even acute PID can be difficult to diagnose, as there is no single conclusive diagnostic test. Currently, PID is identified and treated syndromically because pelvic pain is the only consistent clinical finding. The Center for Disease Control and Prevention (CDC) recommends doxycycline, a broad-spectrum antibiotic, for treatment but doxycycline can cause gastrointestinal irritation and local inflammation leading to an incomplete treatment. Most cases of PID are polymicrobial infections of the tubes and endometrium, which are not accessible to culture due to the difficulty of procuring samples above the naturally contaminated vagina and distal cervix. Given the difficulty of properly diagnosing PID and the limitations and side effects of the current treatments, there is an urgent need for new approaches for improving the accuracy for diagnosis and treatment of PID. We propose a new and practical approach to collect sterile specimen samples from the endometrium for more accurate PID diagnosis, and to treat the reproductive tract locally using doxycycline-loaded nanoparticles. The proposed research presents a novel sterile uterine sampler cover (SUSC) device that can safely and effectively collect uncontaminated specimen samples from the uterus, and also deliver nano-encapsulated drugs directly to the site of infection. The analysis of uncontaminated endometrium samples is expected to provide an understanding of uterine flora in symptomatic and asymptomatic women, and will lead to the identification of infective microbes in symptomatic women for pathogen-specific treatment. The use of nano-encapsulated doxycycline will enable localized drug delivery to lower drug dosage and minimize side effects for the patient. The doxycycline-loaded nanoparticles are characterized and evaluated based on their drug release properties, size distribution, and tissue response in vitro. This research will lead towards a more effective approach for the diagnosis and treatment of PID while freeing women from prolonged systemic treatments and their adverse effects. Moreover, this research will increase our understanding of the uterine biome under various hormonal and pathologic conditions, in symptomatic and asymptomatic women.

The asymptomatic nature of chlamydial infection renders the differential diagnosis of acute and chronic infection difficult. An untreated Chlamydia trachomatis infection can become chronic, result in disease sequelae such as salpingitis and pelvic inflammatory disease (PID), and ultimately culminate in tubal occlusion and infertility. Diagnostic tests for C. trachomatis such as nucleic acid amplification testing (PCR), antigen detection and serological methods have variable performance capabilities with respect to sensitivity, specificity and stage of infection. The use of PCR as a diagnostic tool is somewhat limited, as specimen collection is routinely sampled from the lower genital tract; hence, infections in the fallopian tube where inflammatory damage is most significant, escape detection. Furthermore, PCR can only detect selected Chlamydia DNA sequences from readily accessible sites of the genital tract, and therefore cannot differentiate between acute and chronic infection. Other serological assays aim to discriminate the various stages of C. trachomatis infection through identification of key antigens. The efficacy of these assays however is impeded due to cross-reactivity between chlamydial species and the subsequent antibody response against the target antigen is not restricted to patients with a specific stage of infection. To identify antibody responses capable of differentiating various states of chlamydial infection, samples were collected from both men and women given the variability of immune responses between the two genders. Samples were assigned to a patient group according to infection status and then probed against protein extracts of HEp-2 cells infected with C. trachomatis serovar L2 and HEp-2 cells pre-treated with IFN-γ and infected with C. trachomatis serovar L2. (persistence cell culture) Serological analysis revealed the presence of five antigens (denoted bands A, B, C, D and M) which were shown to be differential between patient groups. Identification of bands B and C by N-terminal sequencing provided two possible candidates for each antigen, ie. CT727 and CT396 (band B) and CT157 and CT423 (band C). In contrast, band M which was unique to males was a PmpB (probable outer membrane protein B) fragment. The four target antigens (CT157, CT423, CT727 and CT396) were expressed as recombinant proteins using autoinduction media and were subsequently probed by both male and female sera to evaluate their diagnostic potential. Results showed that two chlamydial antigenic targets (CT157 and CT727) have the potential to discriminate between acute and chronic C. trachomatis infection. However, since only a small number of samples (n = 3) were used for this aspect of the study, the findings should simply be viewed as preliminary. In females, sensitivity and specificity values were derived using various combinations of the four target antigens into a panel format for the purpose of detecting chronic C. trachomatis infections. The preferred format was B + C with a sensitivity and specificity of 80% and 84% respectively. Using the IFN-γ-mediated persistence model, only two of the five antigenic targets were shown to be differentially expressed. PmpB in males and CT157 (the most likely band C candidate) in females were shown to be up-regulated to varying degrees in samples across the patient groups. We also demonstrated that no other chlamydial antigens are up-regulated during a persistent C. trachomatis infection. In conclusion, although combinations of bands A, B, C, D and M differentiate between male and female patient groups under normal chlamydial growth conditions, during IFN-γ-induced persistence, only bands C (CT157) and M (CT413 - PmpB) are up-regulated thus suggesting a potential role in chronic C. trachomatis infection.

The asymptomatic nature of chlamydial infection renders the differential diagnosis of acute and chronic infection difficult. An untreated Chlamydia trachomatis infection can become chronic, result in disease sequelae such as salpingitis and pelvic inflammatory disease (PID), and ultimately culminate in tubal occlusion and infertility. Diagnostic tests for C. trachomatis such as nucleic acid amplification testing (PCR), antigen detection and serological methods have variable performance capabilities with respect to sensitivity, specificity and stage of infection. The use of PCR as a diagnostic tool is somewhat limited, as specimen collection is routinely sampled from the lower genital tract; hence, infections in the fallopian tube where inflammatory damage is most significant, escape detection. Furthermore, PCR can only detect selected Chlamydia DNA sequences from readily accessible sites of the genital tract, and therefore cannot differentiate between acute and chronic infection. Other serological assays aim to discriminate the various stages of C. trachomatis infection through identification of key antigens. The efficacy of these assays however is impeded due to cross-reactivity between chlamydial species and the subsequent antibody response against the target antigen is not restricted to patients with a specific stage of infection. To identify antibody responses capable of differentiating various states of chlamydial infection, samples were collected from both men and women given the variability of immune responses between the two genders. Samples were assigned to a patient group according to infection status and then probed against protein extracts of HEp-2 cells infected with C. trachomatis serovar L2 and HEp-2 cells pre-treated with IFN-γ and infected with C. trachomatis serovar L2. (persistence cell culture) Serological analysis revealed the presence of five antigens (denoted bands A, B, C, D and M) which were shown to be differential between patient groups. Identification of bands B and C by N-terminal sequencing provided two possible candidates for each antigen, ie. CT727 and CT396 (band B) and CT157 and CT423 (band C). In contrast, band M which was unique to males was a PmpB (probable outer membrane protein B) fragment. The four target antigens (CT157, CT423, CT727 and CT396) were expressed as recombinant proteins using autoinduction media and were subsequently probed by both male and female sera to evaluate their diagnostic potential. Results showed that two chlamydial antigenic targets (CT157 and CT727) have the potential to discriminate between acute and chronic C. trachomatis infection. However, since only a small number of samples (n = 3) were used for this aspect of the study, the findings should simply be viewed as preliminary. In females, sensitivity and specificity values were derived using various combinations of the four target antigens into a panel format for the purpose of detecting chronic C. trachomatis infections. The preferred format was B + C with a sensitivity and specificity of 80% and 84% respectively. Using the IFN-γ-mediated persistence model, only two of the five antigenic targets were shown to be differentially expressed. PmpB in males and CT157 (the most likely band C candidate) in females were shown to be up-regulated to varying degrees in samples across the patient groups. We also demonstrated that no other chlamydial antigens are up-regulated during a persistent C. trachomatis infection. In conclusion, although combinations of bands A, B, C, D and M differentiate between male and female patient groups under normal chlamydial growth conditions, during IFN-γ-induced persistence, only bands C (CT157) and M (CT413 - PmpB) are up-regulated thus suggesting a potential role in chronic C. trachomatis infection.

Introdução: Chlamydia trachomatis (CT) é causa da infecção sexualmente transmitida de origem bacteriana mais comum. Na mulher, a infecção genital pela CT pode causar cervicite, uretrite, endometrite, salpingite. Infecções persistentes ou recorrentes provavelmente representam um importante fator de risco para o desenvolvimento de sequelas associadas, como dor pélvica crônica, gravidez ectópica e infertilidade por fator tubário. A lectina ligadora de manose (MBL), componente doo sistema imune inato, tem importante papel na defesa antimicrobiana, reconhecendo vírus, fungos e patógenos bacterianos. O gene que codifica para a MBL é polimórfico, e a substituição de um único nucleotídeo resulta na produção de uma proteína instável, que é rapidamente degradada. Objetivo: Avaliar se mulheres brasileiras portadoras de um polimorfismo do gene da MBL apresentam diferentes susceptibilidades para a ocorrência de obstrução tubária, na presença ou ausência de uma infecção prévia por Chlamydia trachomatis. Métodos: Em estudo caso-controle, foram avaliadas 75 pacientes com obstrução tubária e 75 pacientes com tubas pérvias, atendidas na Divisão de Ginecologia do Hospital das Clínicas da Universidade de São Paulo (HCFMUSP). Anticorpos IgG anti-CT foram mensurados através de um ensaio de imunoabsorção enzimática para investigar uma infecção prévia pela CT. Para o polimorfismo, realizou-se coleta de células bucais e o DNA extraído foi analisado através de reação em cadeia da polimerase (PCR), digestão de endonuclease e gel de eletroforese, utilizando pares de primers específicos para a região polimórfica. Todo material foi mantido a -80°C e enviado em gelo seco para a Division of Immunology and Infectious Diseases da Weill Cornell Medicine em Nova York. Associações entre genótipos de MBL ou alelos e permeabilidade tubária foram analisadas pelo teste de qui-quadrado de Pearson com ou sem correção de Yates. Resultados: Não houve diferença na detecção de anticorpos da CT entre os grupos. Mulheres com tubas obstruídas tiveram uma prevalência maior do genótipo AB (36%) versus (16%), resultado estatisticamente significativo (p < 0,01). De maneira semelhante, a distribuição do alelo A e do alelo variante B também apresentaram diferenças significantes entre os grupos (p < 0,01). Conclusão: Os achados sugerem, que embora a exposição à Chlamydia trachomatis tenha sido semelhante em ambos os grupos, a presença do alelo variante B do gene que codifica para a MBL aumenta o risco de desenvolvimento da obstrução tubária, subsequente à infecção pela CT ou outros agentes infecciosos. Nas mulheres brasileiras avaliadas a presença de tal polimorfismo genético aumentou a probabilidade de obstrução tubária em consequência de uma infecção do trato genital
Introduction: Chlamydia trachomatis (CT) is the cause of the most common bacterial sexually transmitted infection. In women, genital CT infection may cause cervicitis, urethritis, endometritis, salpingitis. Persistent or recurrent infections probably represent an important risk factor for the development of associated sequelae, such as chronic pelvic pain, ectopic pregnancy and tubal factor infertility. Mannose-binding lectin (MBL), a component of the innate immune system, has an important role in antimicrobial defense, recognizing viral, bacterial and fungal pathogens. The gene coding for MBL is polymorphic and a single nucleotide substitution results in production of an unstable protein, that is rapidly degraded. Objective: To evaluate whether Brazilian women with a polymorphism in the MBL gene present different susceptibilities to the occurrence of fallopian tube damage, in the presence or absence of a previous infection by CT. Method: In a case-control study, 75 patients with tubal obstruction and 75 patients with patent tubes were studied, all seen at the Gynecology Division of the Hospital das Clínicas of the University of São Paulo (HCFMUSP). IgG anti-CT antibodies were measured by enzyme-linked immunoassay to investigate a previous CT infection. For the polymorphism analysis, buccal cells were collected and the extracted DNA was analyzed by polymerase chain reaction (PCR), endonuclease digestion and gel electrophoresis using primer pairs specific for the polymorphic region. All material was maintained at -80 ° C and sent on dry ice to the Division of Immunology and Infectious Diseases at Weill Cornell Medicine in New York. Associations between MBL genotypes or alleles and tubal permeability were analyzed by the Pearson chi-square test with or without Yates correction. Results: There was no difference in CT antibody detection between the two groups. Women with obstructed tubes had a higher prevalence of being positive for the heterogenous genotype AB (36%) versus (16%) (p < 0.01). Similarly, the distribution of the normal A allele and variant B allele were also significant different between the two groups (p < 0,01). Conclusion: The findings suggest that while exposure to CT was similar in both groups of women the presence of the variant MBL B allele increases the risk for development of tubal obstruction, subsequent to a CT or other infection. In the Brazilian women evaluated possession of this genetic polymorphism increased the likelihood that blocked fallopian tubes will be a consequence of a genital tract infection

Research objective: to characterize urogenital tract biocenosis peculiar for women with pelvic inflammatory diseases (PID) through comprehensive assessment of the balance of normal, opportunistic and absolutely pathogenic microflora using “Femoflor screen” reagent kit. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/36583

碩士
中山醫學大學
生化暨生物科技研究所
99
Our purpose here was to detect the association among plasma osteopontin concentration, single nucleotide polymorphisms (SNPs) of osteopontin gene, and pelvic inflammatory disease (PID). The enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were respectively used to measure the plasma osteopontin level and its gene polymorphisms. The level of plasma osteopontin was elevated in PID patients as compared to healthy subjects and decreased significantly after treatment. Plasma osteopontin concentration was significantly correlated with white blood cell (WBC) and neutrophil counts and plasma C-reactive protein (CRP) level in patients with PID. No significant difference was found in the genotypes or alleles distribution of osteopontin SNPs, rs1126616 or rs9138, between patients with PID and normal controls. Plasma osteopontin concentration was not associated with osteopontin polymorphism. When the cutoff level of the plasma osteopontin concentration was set to be 58.53 ng/mL, the adjusted odds ratio of plasma osteopontin for PID risk was 3.87 (95% confident interval: 1.30-11.51). Plasma osteopontin level may act as a prediction marker for PID.

博士
中山醫學大學
醫學研究所
99
Pentraxin 3 (PTX3) plays an important role in innate immune responses and in inflammation disease. The aim of this study was to investigate the diagnostic and prognostic potential of PTX3 in pelvic inflammatory disease (PID) and correlate it with the severity and outcome of PID. In this study, we collected blood specimens from 64 patients with PID before and after treatment and 70 healthy controls and measured the plasma levels of PTX3 using enzyme-linked immunosorbent assay (ELISA) kits. We found that the plasma level of PTX3 expression was elevated in PID patients compared with healthy controls, and decreased significantly after they received treatment. When we set the cutoff level of plasma PTX3 at 2.87 ng/mL, PTX3 had higher sensitivity (84.38 %) and lower false negative rate (15.63 %) than CRP (79.69 % and 20.31 %, respectively) in predicting PID. The level of PTX3 also exhibited a significant correlation with length of hospital stay (r=0.581, p<0.001). Plasma PTX3 concentration not only predicts the presence of PID with lower false negative rate than CRP, but plasma PTX3 concentration is also affiliated with the length of the hospital stay.

碩士
中山醫學大學
生化暨生物科技研究所
96
Pelvic inflammatory disease (PID) is caused by micro-organisms which colonize in the endocervix and ascend to the endometrium and fallopian tubes and become manifestations such as endometritis, pelvic peritonitis, tubal abscess, and salpingitis in the fallopian tube. We speculate that the regulation of cathepsin B and cystatin C is involved the inflammatory process and is related to the progression of PID. Thus, in this study, we sought to determine whether serum cathepsin B and cystatin C were efficient serum markers compared with WBC, neutrophils, and CRP in PID patients. In this study, ELISA analysis was employed to measure the serum levels of cathepsin B and cystatin C before and after routine protocol treatments in PID patients. A significantly increased expression of cathepsin B but decreased expression of cystatin C and significant correlations between neutrophils and cathepsin B, as well as between CRP and cathepsin B, were found in PID patients. Consistently, the ratio of cathepsin B to cystatin C correlated significantly with neutrophils and with CRP in PID patients. Increased expression of cathepsin B but a decreased level of cystatin C and an imbalance between cathepsin B and cystatin C may contribute to the progression of PID. Detection of cathepsin B and cystatin C can provide useful clinical information for PID.

博士
中山醫學大學
醫學研究所
97
Pelvic inflammatory disease (PID) is caused by micro-organisms which colonize in the endocervix and ascend to the endometrium and fallopian tubes and become manifestations such as endometritis, pelvic peritonitis, tubal abscess, and salpingitis in the fallopian tube. However, the role of myeloperoxidases and proinflammatory cytokines in PID is unclear. We therefore determine whether plasma myeloperoxidases and proinflammatory cytokines, interleukin 1beta (IL-1beta), IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were useful plasma markers in PID patients. ELISA and PCR-RFLP were respectively used to measure the plasma levels and genetic polymorphism of myeloperoxidase. Furthermore, Multiplex bead array analysis was used to measure the plasma levels of proinflammatory cytokines in healthy controls as well as in PID patients before and after routine protocol treatments. We discussed the plasma level of myeloperoxidase was elevated in PID patients compared to that in normal controls and decreased significantly compared to that in the same patients after they received treatment. IL-1beta, IL-6, IL-8, and TNF-alpha were statistically elevated in PID patients before they received antibiotic treatment than after they did. However IL-8 was not significantly difference between healthy controls and PID patients. The relatively increased ratio of IL-6 was correlated with the count of WBC (r=0.448, P=0.003), neutrophil (r=0.472, P=0.002), and the level of CRP (r=0.412, P=0.008). We concluded that IL-1beta, IL-6, IL-8, and TNF-alpha may play important roles in the pathogenesis of PID. These biomarkers, particular IL-6, could be useful adjuncts for the clinical diagnosis of PID. Furthermore, elevated expression of myeloperoxidase may be involved in the pathogenesis of PID and could be useful for the diagnosis of PID.

碩士
中山醫學大學
生化暨生物科技研究所
99
To detect the expression of plasma neutrophil gelatinase associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) in patients with pelvic inflammatory disease (PID). Enzyme-linked immunosorbent assay was used to measure the plasma NGAL and NGAL/MMP-9 complex levels. Results: The plasma NGAL or NGAL/MMP-9 complex levels were elevated in PID patients compared with normal controls subjects and decreased significantly after treatment. Pre-treatment plasma level of NGAL was significantly correlated with WBC and neutrophil counts. In PID patients, NGAL/MMP-9 complex plasma level was correlated significantly with NGAL or MMP-9 plasma level. In predicting PID, the sensitivities of NGAL and NGAL/MMP-9 complex were 76.6% and 78.1%, respectively and the negative predictive values were 72.7% and 74.5%, respectively. Conclusions: Plasma NGAL and NGAL/MMP-9 complex may act as diagnostic adjuvant biomarkers for PID. About 80% of PID patients have NGAL or NGAL/MMP-9 complex plasma levels higher than 10.04 ng/ml or 2.33 ng/ml, respectively

Faculty of health Sciences, School of Pharmacy, Msc (Med)Research Thesis.
Objective: To assess the relative cost effectiveness of moxifloxacin once-daily empirical monotherapy and ofloxacin/ metronidazole twice daily combination therapy for the treatment of uncomplicated pelvic inflammatory disease in adult female patients. Design: This is a retrospective cost analysis using data from a clinical trial in order to perform the economic anlysis from a funder perspective. The cost analysis is based on the clinical results of the MAIDEN study which is a prospective, randomized, double-blind, multicentre, multinational Phase III study comparing the efficacy and safety of moxifloxacin 400 mg po od for 14 days with ofloxacin 400mg po bid plus metronidazole 400mg po bid for 14 days in patients with uncomplicated pelvic inflammatory disease. Decision analysis is used to characterise the economic outcomes between groups and provide a structure upon which to base the sensitivity analyses. Published 2004 cost values are used throughout. Cost values for moxifloxacin are based on the retail price of Avelon tablets in South Africa as appears on the Orderwise Retail Pharmacy Ordering System (September 2004). Cost values for the comparator, ofloxacin and metronidazole, are based on the cheapest available generics on the South African market i.e. Zanocin 400 and Metazol 400mg respectively. Method: The cost analysis is based on the clinical results obtained from the MAIDEN study. Patients were enrolled in either the moxifloxacin treatment group (Group A) or the ofloxacin / metronidazole comparator group (Group B). Resource utilization included: - cost for study antimicrobials (total number of doses for the study period) - treatment for adverse events occurring up to 7 days after stopping the study medication - treatment for failures (includes patients continued on antimicrobial therapy after the 14 day course of therapy) - cost of additional physician visits to treat adverse events and treatment failures The primary end-point is the overall cost of treatment per patient as determined by: Clinical response 7 to 14 days after the last dose of study medication (Test-of-Cure visit) Since the clinical findings from the MAIDEN study showed that moxifloxacin treatment was at least as efficacious as ofloxacin/metronidazole treatment, a cost-minimization analysis was performed and the results were analysed according to decision analysis. Decision analysis was used to characterise the economic outcomes between the groups and provided a structure upon which to base the sensitivity analyses. The outcomes were depicted on a decision tree which proportionately determined the cost of treatment per patient in the two treatment groups. Results: No significant differences in clinical success rates were detected. Differences were mainly due to the cost of treating adverse events in the two groups. Costs per patient in the monotherapy vs combination therapy comparisons were R10 847.00 for moxifloxacin and R16 630.00 for ofloxacin/metronidazole treatment. Sensitivity analyses revealed that moxifloxacin monotherapy can be cost effective compared with ofloxacin/metronidazole combination therapy in different situations. Conclusion: Per patient, the cost of drug treatment and treatment of adverse events and clinical relapses was R10 847.00 for treatment with moxifloxacin therapy and R16 630.00 for ofloxacin/metronidazole therapy . In comparison to ofloxacin/metronidazole combination therapy, moxifloxacin monotherapy was therefore cost saving.

碩士
亞洲大學
健康產業管理學系長期照護組碩士在職專班
105
Background: Pelvic inflammatory disease is a common inflammatory disease in women. The inflammatory response can be persistent and systemic, and long-term systemic inflammation is considered as the primary cause of cardiovascular disease. Peripheral arterial disease is the third among cardiovascular diseases associated with atherosclerosis, with its risk of death due to myocardial infarction, stroke, or cardiovascular disease being more than three times that among individuals of the same age group, making it an important health issue. Pelvic inflammatory disease has been reported to be associated with cardiovascular disease; hence, it is likely that pelvic inflammatory disease and peripheral arterial disease will be accompanied by cardiovascular disease. This issue has not yet been reported in Taiwanese population. Therefore, this study investigated the association between pelvic inflammatory disease and peripheral arterial disease. Methods: This retrospective cohort study was conducted using Taiwan National Health Insurance Research Database. The pelvic inflammatory disease group consisted of 66,846 newly diagnosed females aged 13–50 years recruited from 2000 to 2010, and the nonpelvic inflammatory disease group consisted of the same number of control subjects with a propensity score matched to 1:1 ratio and matched according to age, date of disease diagnosis, and associated comorbidities. Both groups were monitored till the end of 2011, and the incidence of peripheral arterial disease was determined. Data were analyzed using single variable and variable Cox proportional hazards regression model to assess crude hazard ratio, adjusted hazard ratio, and 95% confidence interval (CI). All statistical analyses were conducted using SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA), with p values <0.05 being defined as statistically significant. Results: In terms of age stratification, the highest incidence of pelvic inflammatory disease (51.6%) was found in patients aged 13–29 years. The incidence of peripheral arterial disease was 1.18 times higher in subjects with pelvic inflammatory disease than that in the nonpelvic inflammatory disease group (7.76/10,000 vs 6.55/10,000 PY), with the adjusted hazard ratio of 1.54 (95% CI = 1.35–1.76). The risk of peripheral arterial disease was 1.78 times (95% CI = 1.33–2.38) among patients aged 30–39 years; the risk also reached 1.68 times among subjects with no risk of peripheral arterial disease and without comorbidities. In addition, patients with pelvic inflammatory disease receiving medical care (more than seven times a year) had a significantly increased risk of peripheral arterial disease (adjusted risk ratio = 22.7, 95% CI = 17.7–29.0). Conclusion: The findings of this study suggest that patients with pelvic inflammatory disease develop an increased risk of peripheral arterial disease. Appropriate monitoring of women suffering from pelvic inflammatory disease is necessary to assess the possibility of its association with cardiovascular disease. Early diagnosis and treatment and long-term care can reduce the usage of medical resources, which could also improve the quality of healthy living.

碩士
中山醫學大學
醫學研究所
102
Abstract Backgrounds: To investigate the concentrations of plasma growth arrest-specific protein 6 (Gas6) and its solubletyrosine kinase receptor sAxl in women with pelvic inflammatory disease (PID) and their association with clinicaloutcomes of PID. Methods: Blood specimens were consecutively collected fromthe 64 patients with pelvic inflammatory disease (PID) before and after treatmentand 70 healthy women in university hospital. Concentrations of plasma Gas6 and sAxl were detected usingenzyme-linked immunosorbent assay (ELISA). Results: The concentration of plasma growth arrest-specific protein 6 (Gas6) and solubletyrosine kinase receptor sAxl was significantly increased in the patients with PID comparedto the healthy controls, and then reduced significantly after treatment. Gas6 was significantly correlated withsAxl. When we selected 7.5 and 15.2 ng/ml as the cutoff concentration of plasma Gas6 and sAxl to detect PID respectively,the sensitivities of Gas6 and sAxl were 76.6% and 75.0%.When Gas6 and sAxlwere combined, the sensitivityrose to 92.2%. They were not related to the incidences of tubo-ovarian abscesses and surgery, which were,however, significantly associated with length of hospital stay. Conclusions: Novel application of Gas6 or sAxl in combination had a high sensitivity to detect PID and is importantin order to prevent severe sequelae.

The association between being infected with the sexually transmitted infections (STIs), Chlamydia trachomatis or Neisseria gonorrhoeae and developing pelvic inflammatory disease (PID) is supported in the literature. Research also demonstrates an association between repeat infections with chlamydia or gonorrhea and acquiring PID. While there is some information from Canada on this topic, the majority of the research is from the United States and abroad. Additionally, there are few studies that have been able to examine the risk of acquiring PID utilizing a prospective study design. The purpose of this study is to identify the risk of women in Manitoba acquiring PID from one or more episodes of genital chlamydia or gonorrhea. The length of time following a genital chlamydial or gonococcal infection where PID develops is explored. Obtaining information on the risks of acquiring PID, among women in Manitoba with genital chlamydia or gonorrhea, has important policy implications such as early detection and screening of STIs, treatment procedures, partner notification and contact tracing. A surveillance system framework was used to guide the study. The data were acquired by linking administrative databases from Cadham Provincial Laboratory and Manitoba Health. Three cohorts of women were chosen, based on their history of testing positive or negative for STIs. Quantitative data analysis was completed through the use of the Statistical Analysis Software (SAS) program. Descriptive statistics and frequency distributions were completed for each variable to become familiar with the data. Since this is a cohort study, incidence rates and measures of association, such as the relative risk, were completed. Tests of statistical significance were also calculated. Study findings indicate that l5 - 24 year old women, in Manitoba with documented infections of genital...

This study is about evaluating the effectiveness of training in syndromic management ofSTDs. The purpose of this study was to fmd out to what extent the STD training programme had been implemented. A stratified sample of twenty-two primary health care clinics in the Port Shepstone region was used. Twenty-two professional nurses rendering STD management in the clinics were observed. Data-gathering was done through a clinic inventory obtained by interviewing the sister-incharge, observation of professional nurses providing treatment to STD patients, interviews with professional nurses to assess their knowledge of the syndromic approach, and exit interviews with patients treated at the clinic. The fmdings suggest that certain areas in the STD training need to be emphasized, such as vaginal speculum and bi-manual examinations. It is recommended that certain negative aspects which hinder effective STD management, like staff shortages and lack of equipment be given attention.
Health Studies
M.A. (Health Studies)

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
A infertilidade define-se como a incapacidade de obter uma gravidez após 12 meses de relações sexuais regulares e desprotegidas, sendo que a causa mais comum de infertilidade feminina é a patologia tubária. Quando uma patologia compromete o normal funcionamento das trompas provocando infertilidade, designamos este fenómeno por fator tubário da infertilidade, que é responsável por cerca de 25% a 35% de todos os casos de infertilidade feminina. Os determinantes etiológicos do fator tubário da infertilidade podem ser adquiridos, como as infeções, endometriose, trauma cirúrgico, pólipos ou miomas, ou podem ser congénitos, como a agenesia ou duplicação tubária.O diagnóstico de infertilidade feminina deve iniciar-se com a realização da história clínica e exame físico completo. Os métodos de diagnóstico mais utilizados atualmente são a ecografia endovaginal, a histerossalpingografia, a histerossonografia contrastada, a laparoscopia com prova de cromotubação e a salpingografia seletiva.As abordagens terapêuticas que se têm vindo a desenvolver englobam tanto procedimentos cirúrgicos como a procriação medicamente assistida, nomeadamente a fertilização in vitro.Ao longo das últimas décadas avanços científicos significativos têm sido alcançados, nomeadamente no que concerne ao fator tubário da infertilidade, embora ainda não sejam totalmente conhecidos os mecanismos subjacentes à patogenicidade de alguns fatores etiológicos. É ainda necessário apurar a eficácia de alguns procedimentos terapêuticos utilizados para tratar mulheres com fator tubário da infertilidade e as suas possíveis implicações futuras na gravidez. Desta forma, torna-se necessário compreender a sua epidemiologia, etiologia e fisiopatologia, assim como determinar quais são os métodos de diagnóstico mais adequados e quais as abordagens terapêuticas existentes atualmente.
Infertility is defined as the inability of achieving a pregnancy after 12 months of regular and unprotected intercourse. The most common cause of female infertility is associated to the pathology of the fallopian tubes. When a pathology compromises the normal functioning of the tubes causing infertility, we name such phenomenon by tubal factor infertility which is responsible for about 25% to 35% of all the cases of female infertility.The several etiologies of tubal factor infertility can be acquired, such as infections, endometriosis, surgical trauma, polyps or myomas, or they may be congenital, such as agenesis or tubal duplication.The diagnosis of female infertility should begin with a clinical history and a complete physical examination. Currently the most common used diagnosis procedures are the endovaginal ultrasonography, hysterosalpingography, hysterosalpingo contrast sonography, laparoscopy with chromopertubation and selective salpingography.The therapeutic approaches that have been developed include both surgical procedures such as medically assisted procreation, namely in vitro fertilization.For the last decades, significant scientific advances have been achieved, namely concerning tubal factor infertility, although the mechanisms underlying the pathogenicity of some etiological factors are not yet fully understood. It is also necessary to determine the efficacy of some therapeutic procedures used to treat women with tubal factor infertility and their possible future implications in pregnancy. Therefore, it is necessary to understand its epidemiology, etiology and pathophysiology, as well as to determine the most appropriate diagnostic methods and the current therapeutic approaches.