No description available.

This observational study compared bone health biomarkers, bone mineral density (BMD),dietary habits, and physical activity levels of men (n=31) and non-estrogen supplementing postmenopausal women (n=23) divided according to duration of proton pump inhibitor (PPI) therapy; more than 5 years (n=16), less than 5 years (n=15), and no PPI therapy (n=23). The shortest duration of PPI therapy was 2 months and the longest duration of PPI therapy was 25 years with a mean duration of 7.5 years. No significant differences were found between measures of spine BMD, urinary deoxypyridinoline (bone resorption), urinary calcium and magnesium, serum osteocalcin (bone formation), serum parathyroid hormone, serum magnesium, serum 25 hydroxyvitamin D3, dietary and supplement intake, or physical activity levels. However, mean hip BMD was higher in females than in males in participants who took PPI therapy for any duration. In the no PPI therapy group, hip BMD was not significantly different between genders. These results suggest that there may be no measurable or clinically significant negative effects of long term PPI therapy on bone health. However, men may be at higher risk of hip fracture when taking long-term PPI therapy than women.

Clostridium difficile (C. difficile) is a gram positive, anaerobic, spore forming bacterium. C. difficile infections are triggered by dysbiosis of the intestinal microbiome linked to age, immune status, and medication; particularly use of antibiotics and proton pump inhibitors (PPI). The spore forming nature of the bacteria gives it the ability to persist in the environment for long periods of time and makes it impervious to many commonly-used hospital cleaning and disinfection products. C. difficile, along with Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus (VRE) are some of the leading multi-drug resistant hospital acquired infections in the United States. Environmental contamination and patient susceptibility are hypothesized as major contributors to infection transmission in a healthcare setting. We conducted a cross-sectional pilot study aimed at determining the bioaerosol concentration of C. difficile present in the toilet plume of C. difficile infected patients’ rooms. Patient rooms within the University of Iowa Hospital and Clinics (UIHC) were sampled using a customized bioaerosol air impactor device. Environmental samples were collected before and after flushing the toilet to determine the pre-flush and post-flush levels of aerosolized bacteria. Particle density was collected during both pre and post-flush sampling. Activity levels in the rooms were recorded as a potential confounding variable. A total of 144 environmental samples were collected in 24 rooms. Clostridium difficile was detected in two of the twenty-four rooms (8%). There was a 12% (9/72) positive culture rate pre-flush compared to 23% (19/72) post-flush. Wilcoxon rank sum tests revealed a significant increase in particle concentration at the 5.0µm and 10.0µm size between rooms that produced a bacterial culture compared to rooms that did not (p-values 0.0095 and 0.0082 respectively). There was no significant association between the amount of activity in the room and detectable bioaerosol production (p-value=0.605). Next, we performed a randomized control trial of hospital privacy curtains with antimicrobial properties to determine their ability to resist pathogenic bacterial contamination in an intensive care unit setting. Rooms within the surgical and neurological intensive care unit at UIHC were randomized to receive impregnated curtains, impregnated curtains plus Fuzion hypochlorite spray, or standard control curtains. MRSA, VRE, Pseudomonas spp. and Acinetobacter spp. were the four most frequently cultured pathogenic species. Time to event (contamination) analysis identified a significant difference in time to pathogenic contamination between the control curtains and the impregnated curtains post spray (p-value<0.001). The impregnated curtains post Fuzion spray also grew significantly less colonies of bacteria compared to the control curtains (p-value<0.001). After evaluating environmental risk factors that contribute to Clostridium difficile infection, patient related risk factors for infection were evaluated. Proton pump inhibitors are a class of gastric acid reducers that work by reducing the amount of hydrogen ions produced in the stomach. Recent evidence suggests that prolonged use could negatively affect the intestinal microbiome making it more susceptible to enteric pathogens. A nested case control study was done to determine the association between PPI medication duration and C. difficile infection. Fecal microbiome diversity was analyzed via logistic regression in relation to the development of Clostridium difficile infection. A co-morbidity score was created to adjust for other microbiome altering conditions. PPI duration remained a significant predictor of infection after adjusting for the microbiome influence (p-value=0.0123). Environmental contamination remains a significant risk factor for the transmission of hospital acquired infections including C. difficile. Toilets flushing has been shown to produce pathogenic bioaerosols in the healthcare setting. Hospital privacy curtains have been shown to routinely be contaminated with pathogenic bacteria including other gastrointestinal bacteria that could increase susceptibility to C. difficile infection. PPI medication, which is frequently prescribed in the hospital, has been shown to increase the risk of C. difficile infection, although specific microbiome changes could not be identified.

Over half of patients with gastroesophageal reflux disease (GERD) report nocturnal symptoms. Proton pump inhibitors (PPIs) are the main medications used to treat GERD. Multichannel intraluminal impedance with pH (MII-pH) monitoring is the most sensitive method for detection and characterization of GERD. The aim of this study was to assess and compare reflux frequency in patients with refractory GERD symptoms on and off PPI therapy during the nocturnal recumbent period, as assessed by MII-pH testing. We analyzed 24-hour MII-pH studies performed in 200 patients monitored either on twice-daily (n=100) or off (n=100) PPI therapy. Demographic analysis of the on-therapy group revealed a mean age of 52 years (24-78 years) with 37% males, and the off-therapy group revealed a mean age of 49 years (18-84 years) with 40% males. All studies were interpreted to assess and characterize the number of acid and nonacid reflux episodes in the nocturnal recumbent period identified by each patient on an overnight recorder (Zephyr, Sandhill Scientific, Inc., Highlands Ranch, CO, USA). The nocturnal recumbent period was the period documented by patients during which they lie in the recumbent period at night to sleep with average periods lasting 456 and 453 minutes for patients on and off PPI therapy. There were more mean recumbent reflux episodes in the on-therapy group in comparison with the off-therapy group (3.76 mean reflux episodes [mre] per patient in the recumbent vs. 2.82 mre); the difference was not statistically significant (P=0.187). When the reflux events are classified into acid and non-acid reflux episodes, the relative occurrence of acid reflux events is less in the on-therapy group (P=0.047), while the off-therapy group have fewer nonacid reflux episodes (P=0.003). PPIs decrease the acidity of esophageal refluxate but do not decrease the relative frequency of reflux episodes in the recumbent position in patients with refractory GERD despite twice-a-day treatment with PPI therapy. The explanation for the finding of numerically increased, although not statistically significant, amount of reflux episodes in the PPI treatment group in this study, and previous studies is unclear and warrants further evaluation.

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第19277号 / 社医博第68号 / 新制||社医||9(附属図書館) / 32279 / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 松原 和夫, 教授 今中 雄一, 教授 髙橋 良輔 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24478号 / 医博第4920号 / 新制||医||1062(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 山本 洋介, 教授 近藤 尚己, 教授 柳田 素子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Orientador: José Ricardo de Arruda Miranda / Resumo: A via oral de administração de fármacos é a mais utilizada devido a maior aceitação pelo paciente e sua fácil administração. Dentre as estratégias de sistema de liberação de fármacos estão os comprimidos revestidos com polímero pH-dependente, da qual o Eudragit E-100 é um polímero de revestimento protetor solúvel em pH <5, utilizado em formas farmacêuticas sólidas para liberação do fármaco no ambiente gástrico. Para que ocorra a liberação do fármaco é necessário que o comprimido revestido passe por processos que antecedem a absorção, tal como a dissolução do revestimento e desintegração. Sendo assim, se ocorrer mudanças no pH fisiológico o processo de dissolução do revestimento gastrossolúvel pode ser comprometido e consequentemente alterar a biodisponibilidade do fármaco. Diante deste cenário, é de grande importância realizar pesquisas que explorem a influencia do aumento do pH gástrico na biodisponibilidade de um fármaco, contido em comprimido com revestimento pH-dependente administrado concomitantemente. Nesta proposta consiste em empregar a Magnetofarmacocinética (MgPK) para avaliar a influencia da alteração do pH gástrico provocado pelo tratamento com omeprazol no processo de liberação de um fármaco modelo administrado pela via oral em comprimidos revestidos com Eudragit® E-100. Foi produzido um lote de comprimidos magnéticos revestidos com Eudragit® E -100 contendo 500 mg de ferrita e 100 mg de metronidazol. O lote foi avaliado através de testes farmacotécnicos e avalia... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The oral route of drug administration is the most used due to the greater acceptance by the patient and its easy administration. Among the drug delivery system strategies are tablets coated with pH-dependent polymer, which aim to improve the stability of the drug, mask taste and odor. Eudragit E-100 is a protective coating polymer soluble at pH <5, used in solid dosage forms to release the drug into the gastric environment. For the drug to release, it is necessary that the coated tablet undergo processes that precede absorption, such as the dissolution of the coating and disintegration. Therefore, if changes in physiological pH occur, the dissolution process of the gas-soluble coating may be compromised and consequently change the bioavailability of the drug. In view of this scenario, it is of great importance to conduct research that explores the influence of the increase in gastric pH on the bioavailability of a drug, contained in a tablet with a pH-dependent coating administered concomitantly. In this proposal, it consists of using Magnetopharmacokinetics (MgPK) to evaluate the influence of gastric pH changes caused by treatment with omeprazole in the process of releasing a model drug administered orally in tablets coated with Eudragit® E-100. Batch of magnetic tablets coated with Eudragit® E-100 containing 100 mg of metronidazole was produced. The batch was evaluated through pharmacotechnical tests and evaluated according to the dissolution profile. For in vivo experiment... (Complete abstract click electronic access below) / Doutor

Proton pump inhibitors (PPIs) are commonly coadministered with clopidogrel, an antiplatelet agent, to patients with acute coronary syndrome (ACS). Mechanistic studies suggest that PPIs have the potential to competitively inhibit the bioactivation of clopidogrel and may attenuate its antiplatelet action in the body. The clinical implications of this drug-drug interaction have been extensively studied; however reported findings are inconsistent. More recently, several studies have questioned whether PPIs are associated with adverse cardiovascular events independent of clopidogrel. Given that PPIs and clopidogrel are widely used, it is critical to better understand the clinical impact of the concomitant treatment with both drugs. This thesis includes four studies that investigate the clinical effects of the drug-drug interaction between clopidogrel and PPIs. Chapter 2, a systematic review and meta-analysis, summarizes findings from 118 studies. Findings do not provide strong evidence for an association between adverse cardiovascular events and the use of PPIs when used alone, in combination with clopidogrel, or in combination with other antiplatelets. Chapters 3, 4, and 5 present analyses of real-world data comprised of electronic medical records. Results of these analyses demonstrate 1) that the concomitant use of clopidogrel and PPIs among inpatients was consistent with clinical guidelines suggested by the FDA (Chapter 3); 2) a lack of association between PPI use vs nonuse and four adverse cardiovascular outcomes among clopidogrel users (Chapter 4); and 3) a lack of association between PPI use vs nonuse and adverse cardiovascular outcomes among prasugrel users or ticagrelor users (Chapter 5). Collectively, our findings do not provide evidence of an elevated risk of adverse cardiovascular outcomes with the combined use of PPIs and clopidogrel. Although pharmacodynamic and pharmacokinetic studies have demonstrated an interaction between these two drugs, our findings support the opinion that the biological interaction does not translate into adverse clinical events among patients with acute coronary syndrome.

No description available.

No description available.