Injury and illness associated with drugs are major problems in Australia and around the world, despite significant developments in the area of adverse drug reaction (ADR) decision support technology. The aims of this thesis are: to investigate the ADR decision domain; to determine factors that may assist in the prevention, detection and management of ADRs; and, to inform the pre-requirements analysis phase of the development of decision support systems. An approach has been taken that permits open and grounded study of the decision environment. This approach can then be used to frame and inform the design of an ADR decision support system. Fifteen case studies that comprise self selected consumers, the treating medical practitioner/s and expert perspectives of a single instance of an ADR (fifteen in-depth consumer interviews, eight in-depth medical practitioner interviews and 30 expert written questionnaires), have been collected and analysed using a grounded theory approach, a symbolic interactionist theoretical framework and a social constructionist epistemology. The analysis was performed from three perspectives: individual case study analysis (all interviews for an instance of an ADR); group analysis (consumer, medical practitioner and expert views) and analysis combining the individual case studies and groups of data. Concepts, themes and theory have emerged from these data in the following areas: • the contribution of the differences in understanding of the core concepts within this domain, to misunderstandings between decision-makers; • the consumer as a diagnostic decision-maker in the ADR decision domain; • differential diagnostic strategies used by the consumers and medical practitioners; • complexities in the ADR decision domain that make diagnosis difficult; • the role of ADR information in consumer and medical practitioner decision-making; • decision types used by consumers and medical practitioners in the ADR decision domain; • resources used by consumers, medical practitioners and experts to inform their ADR decisions; • decision-making with partial knowledge of the consumer case history, drug behaviour and diseases; • the impact of suspected ADRs on consumers and on future decision-making; • medical practitioner/consumer decision-making models; and, • reasons for low ADR reporting and the impact on the development of new ADR knowledge. The results above suggest the following: • The ADR decision domain is more complex than the current ADR decision support focus and that broadening this focus may assist in providing a more complete and useful decision support solution. • Improving the prevention, detection and management of ADRs requires more than providing prescribers with up to date ADR information. Other important factors are sharing of information, awareness of the role of the consumer, a collaborative approach between the consumers and medical practitioners, and generation of new ADR knowledge. • A grounded theory analysis of case study data using the theoretical perspectives of social constructionism and symbolic interactionism provided insight into this domain from the perspectives of multiple decision-makers. This may be an approach that can be used by systems analysts to inform the requirements analysis phases of decision support within other domains. The results of this qualitative work are preliminary. Future work is required to confirm and expand these results. / Doctor of Philosophy

Mucositis manifesting as diarrhoea is a common side effect of chemotherapy which remains poorly understood. It is one of a number of manifestations of alimentary mucositis, which affects the entire gastrointestinal tract. The exact number of patients that are affected by diarrhoea as a result of treatment is uncertain, although it is believed that approximately 10% of patients with advanced cancer will be afflicted. Despite advances in the understanding of oral and small intestinal mucositis over recent years, large intestinal mucositis, including diarrhoea, has not been well defined and the underlying mechanisms of the condition are yet to be established. The majority of the literature available concerning diarrhoea is based on clinical observations, with very little basic research existing. However, from the research conducted, it is likely that the intestinal microflora and mucins play a role in the development of chemotherapy-induced diarrhoea. This thesis will examine in detail what is known about the mechanisms of chemotherapy-induced diarrhoea (CID). Furthermore it will explore the potentially important relationship between intestinal microflora, the luminal environment and the subsequent development of chemotherapy-induced mucositis and diarrhoea. 5-Fluorouracil (5-FU) is a commonly used chemotherapy agent in clinical oncology practice. Two of its major side effects are mucositis and diarrhoea. The structure of mucins offers mucosal protection, and allows maintenance of intestinal flora by providing attachment sites and preventing bacterial overgrowth and/or penetration. Following treatment with 5-FU, we showed decreases in Clostridium spp., Lactobacillus spp. and Streptococcus spp., and an increase in Escherichia spp. in the jejunum. In the colon, 5-FU caused decreases in Enterococcus spp., Lactobacillus spp. and Streptococcus spp. Real time PCR of faecal samples showed decreasing trends in Lactobacillus spp. and Bacteroides spp., and an increasing trend in E. coli. Significant increases (p<0.05) were seen in Clostridium spp. and Staphylococcus spp. at 24 h. Goblet cell numbers decreased significantly in the jejunum from 24-72 h, with a significant increase in the percentage of cavitated goblet cells, suggesting 5-FU treatment causes significant changes in intestinal flora and mucin secretion in rats. These changes could result in systemic effects, and in particular may contribute to the development of chemotherapy-induced mucositis. Irinotecan causes cholinergic and delayed onset diarrhoea in patients, in which β-glucuronidase produced by gut bacteria is thought to be involved. Diarrhoea was observed in treated rats, as expected, following irinotecan treatment. β-glucuronidase expression increased in the jejunum and colon. Faecal flora changed quantitatively after treatment also, with increases in E. coli, Staphylococcus spp., and Clostridium spp. (all β-glucuronidase producing), and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (β-glucuronidase producing, major component of intestinal flora), suggesting that irinotecan-induced diarrhoea may be caused by an increase in β-glucuronidase producing bacteria. However, the increase in bacteria may also be caused by irinotecan, further exaggerating the toxicity of the drug, and emphasising the need for these specific bacteria to be therapeutically targeted for successful treatment regimens to be accomplished. Mucus production appears to be increased after irinotecan treatment, which may contribute to the development of diarrhoea. Goblet cells were demonstrated to decrease significantly after irinotecan treatment. However, mucin secretion increased. Mucin expression changed significantly after treatment. Muc2 and Muc4 decreased significantly in the villi of the jejunum after treatment, Muc2 and Muc4 decreased significantly in the crypts. Muc2 decreased significantly in the colon. This indicates that irinotecan causes an increase in mucin secretion and a net decrease in mucin-producing goblet cells, and the expression of Muc2 and Muc4 in the gastrointestinal tract is altered following treatment. Increased mucin secretion is likely to be related to altered mucin expression, and may contribute to chemotherapy-induced diarrhoea. To determine if the changes to the intestinal microflora caused by chemotherapy could be translated to the clinic, a pilot clinical study was carried out. Sixteen patients experiencing CID were recruited to the study with two control subjects. A large proportion of patients (75%) demonstrated a reduced anaerobic component of their faecal microflora. A reduced diversity of species was also observed in patients. The majority of patients exhibited decreases in Clostridium spp., Lactobacillus spp. and Bifidobacterium spp., whilst all patients exhibited decreases in Bacteroides spp. and Enterococcus spp. Patients receiving antibiotics did not exhibit any marked differences to patients not receiving antibiotics. This indicates that the results observed in the animal studies are clinically relevant, and further research into this area should be undertaken. CID is associated with marked changes in the intestinal microflora. These changes may result in diminished bacterial functions within the gut, altering gut function and initiating intestinal damage, resulting in the onset of diarrhoea. In conclusion, there is clear evidence demonstrating chemotherapy treatment results in changes to the intestinal microflora and mucin secretion, which may be responsible in part for the development of severe mucositis and diarrhoea. Irinotecan toxicity may be compounded by the increase in β-glucuronidase producing bacteria. The intestinal flora of cancer patients experiencing CID is also noticeably different to that of healthy subjects. Irinotecan causes changes to mucin secretion, and the specific expression of Muc2, Muc4 and Klf4, suggesting that secretory control by the enteric nervous system may also be affected by chemotherapy. This research has extended the understanding of chemotherapy-induced mucositis and diarrhoea, complex side effects of chemotherapy. However, new areas for future research have also been identified. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352119 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2009

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2007. / Härtill 5 uppsatser.

Background Empirical research on how and why nutritional supplements (including vitamin/mineral supplements and herbal supplements) are being taken by middle-income populations in South Africa is lacking. This study quantifies the types of nutritional supplements being taken. It unpacks beliefs regarding benefits and risks. This information is useful for healthcare practitioners in similar settings as it could affect their practice of history taking and alert practitioners to the need to know more about nutritional supplement benefits and risks. The information could be used to influence policy regarding advertising and labelling of nutritional supplements. Method The study was a cross-sectional survey. An anonymous self-completed structured questionnaire was completed by 123 participants attending a medical centre during the data collection period. Face-to-face semi-structured interviews were conducted on 16 participants to gather qualitative information. Results Nutritional supplements were widely taken in this questionnaire sample (59%). Consumption was not related to age, language, ethnic group, education and smoking, but nutritional supplements were more commonly used by women and higher income groups. Women who felt they had fair/poor health, women with chronic medical conditions, especially those with depression or women on chronic prescription medication were more likely to take nutritional supplements than those without these characteristics. Wellness, treating tiredness and short-term disease prevention were the most common reasons for taking the supplements, although research proving these benefits is lacking. Chronic disease prevention was an uncommon reason for consumption. Participants were mostly unaware of possible drug interactions and side-effects and therefore felt it unnecessary to inform their practitioner of consumption habits. Conclusion Healthcare professionals should include a nutritional supplement question in their routine history taking, especially when prescribing chronic medication and in the presence of chronic conditions. They should be knowledgeable regarding efficacy, safety, possible side-effects and drug interactions of commonly consumed nutritional supplements in order to advise patients appropriately. Further empirical research is needed into proven benefits of nutritional supplements.

Orientador : Patrícia de Carvalho Mastroianni / Banca: Leonardo Régis Leira Pereira / Banca: Natália Valadares de Moares / Resumo: Introdução. O omeprazol é amplamente administrado e, na maioria das vezes, o uso é efetivo e seguro. No entanto, estudos avaliaram que o omeprazol foi o medicamento mais relacionado com a admissão hospitalar devido RAM. Tais RAM talvez possam ser explicadas devido ao uso abusivo ou prescrição irracional de omeprazol. Todavia, não foi avaliado o risco e o benefício do uso profilático do omeprazol, considerando o uso aprovado e o uso não aprovado, e as consequências para a segurança do paciente. Objetivo. Identificar e avaliar o risco de ocorrência de EAM e o benefício através da efetividade do uso profilático de omeprazol em pacientes internados. Método. Conduziu-se um estudo coorte observacional de agosto a outubro de 2013 e dezembro/2013 a maio/2014, no Hospital Estadual Américo Brasiliense. Os pacientes internados foram classificados em três grupos: a) uso de omeprazol profilático aprovado, b) uso de omeprazol profilático não aprovado; c) não uso de omeprazol. Foram excluídos os pacientes que fizeram uso de omeprazol não profilático. Os pacientes foram monitorados diariamente com auxílio do roteiro de investigação adequado previamente. Os dados foram tabulados segundo a presença ou ausência de efetividade e de eventos adversos nos três grupos. Resultados. Foram monitoradas 427 hospitalizações, sendo 136 expostos ao omeprazol profilático não aprovado e 52 expostos ao omeprazol profilático aprovado. Identificaram-se apenas dois casos de suspeita de inefetividade e 14 de eventos adversos. Observou-se diferença significativa na concentração sérica da creatinina e ureia para os pacientes que usavam omeprazol profilático aprovado. Conclusão. Há duas vezes mais pacientes expostos ao omeprazol profilático não aprovado comparado ao uso aprovado. Não houve associação do omeprazol profilático com fator de risco, no entanto, houve diferença significativa no... / Abstract: Introduction. Omeprazole is a widely used drug; in most cases, it is effective and safe. However, studies have found omeprazole to be the drug most frequently related to hospital admissions due to adverse drug reactions (ADRs). The ADRs could have occurred as a result of abuse or irrational prescribing of omeprazole. Despite that possibility, the risks and benefits of prophylactic omeprazole considering the approved and off-label uses and the potential consequences for patient safety have not been assessed. Objective. To identify and assess the risk of adverse drug events and the benefit provided by the effective use of prophylactic omeprazole in hospitalized patients. Methods. This observational cohort study was conducted from August to October 2013 and December 2013 to May 2014 at the Américo Brasiliense State Hospital. The inpatients were classified into three groups: a) approved use of prophylactic omeprazole b) off-label use of prophylactic omeprazole, and c) not using omeprazole. Patients who used no prophylactic omeprazole were excluded. The patients were monitored daily with the aid of a pre-established research protocol. Data were tabulated according to drug effectiveness or ineffectiveness and presence of adverse events in the three groups. Results. A total of 427 hospitalized patients were monitored in the study. Of these, 136 patients were exposed to prophylactic omeprazole used off-label and 52 exposed to on-label use of prophylactic omeprazole. Two cases of suspected ineffectiveness and 14 adverse events were recorded. There was a significant difference in serum creatinine and urea for patients using on-label prophylactic omeprazole. Conclusion. There are twice as many patients using off-label prophylactic omeprazole as patients using it for approved indications. There was no association of prophylactic omeprazole with risk factors, but there was a significant difference in the increase in serum creatinine and urea for ... / Mestre

Leflunomide is widely prescribed for Rheumatoid Arthritis (RA) patients in China. However, a number of RA patients still demonstrated progressive bone erosion (PBE+) after receiving Leflunomide in our clinical data. Moreover, the PBE+ is predicted by high baseline serum CRP level (CRPBH). Further, the changes of serum bone resorption marker (Tartrate-resistant acid phosphatase 5b, TRAP5b) strongly correlated with those of CRP in PBE+ RA patients during Leflunomide treatment. Those were consistently observed in collagen-induced-arthritis (CIA) rats. To precisely address the issue, we screened a series of marketed drugs combined with Leflunomide to inhibit CRP production and CRP-related osteoclastic signaling pathway using bioinformatics analysis. Ligustrazine was postulated as an optimal candidate drug. In vitro studies demonstrated that the combination of Ligustrazine and Leflunomide not only suppressed hepatic CRP production, but also suppressed CRP-related osteoclastic signaling and osteoclast activities. In vivo studies showed that the combination attenuated bone erosion in CIA rats. Further, the randomized parallel controlled clinical trial in 120 CRPBH RA patients showed that the combination therapy reduced serum CRP levels and attenuated bone erosion in those patients (ChiCTR-TRC-10001014). Together, this work presents a precision combination therapy for PBE+ in CRPBH RA patients.

Stroke is one of the most common causes of disability and death worldwide. The most commonly experienced stroke in the clinical setting is focal ischaemia in which the middle cerebral artery (MCA) is occluded and leads to a complex series of various pathophysiological pathways that ultimately lead to neuronal cell death. Several studies have been conducted on various therapeutic agents in the search for a neuroprotective drug and various animal models have been used to carry out this research. While theanine, a component of green tea and minocycline, a tetracycline antibiotic, have been shown to possess some neuroprotective properties, the mechanisms by which these two agents carry out these effects still remains unclear. The objectives of this study were to investigate the mechanisms by which these drugs carry out these neuroprotective effects and their neuroprotective ability in a MCA occlusion model of focal ischaemia. Ischaemia leads to oxidative stress due to the imbalance of free radicals and the endogenous antioxidant defence system. An antioxidant assay using the stable 2, 2-diphenyl-1-picrylhydrazyl (DPPH●) radical was used to assess the antiradical properties of each drug. It was found that minocycline showed superior antioxidant activity in vitro when compared to theanine. Further studies on the drugs‟ ability to attenuate the Fenton reaction (in which iron catalyses the formation of reactive species) were elucidated using electrochemical analysis, UV/VIS studies, ferrozine and ferritin assays. It was found that minocycline, in contrast to theanine, was able to bind to iron ions and thus potentially prevent the participation of iron in metal catalysed radical reaction. The antioxidant activity of both drugs was further investigated by assessing their effect on cyanide-induced superoxide generation and quinolinic acid (QA)-induced lipid peroxidation (LP). Experimental evidence shows that both drugs had no significant effect on the generation of superoxide in vitro and that there was a significant decrease in LP for minocycline in vitro and theanine in vivo. The metal binding and antioxidant properties were postulated to be a possible mechanism through which these agents reduced lipid peroxidation. A study was conducted to determine the effects of the drugs on the biosynthesis of the neurotoxin, QA and it was found that minocycline increases the levels of holoenzyme activity of tryptophan-2, 3-dioxygenase (TDO) in vitro and that theanine reduces the levels of the same enzyme in vivo after treatment for 10 days. TDO is the enzyme that converts tryptophan to other products that enable enzymatic activity to change it to QA. Minocycline was thought to bring about this effect as it has been shown from preceding experimental studies that it is an effective reducing agent. Theanine on the other hand is hypothesised to bring about a reduction in holoenzyme activity by changing the binding of tryptophan to the enzyme or affecting the radicals that participate in the enzymatic degradation of tryptophan. A focal ischaemic model of stroke was induced by occluding the MCA. Histological examination of the hippocampus post -ischaemia shows a reduction in the size of the infarct after pre-treatment with minocycline only. A further study into the effects of the drugs on the generation of superoxide and on the levels of the endogenous glutathione after a stroke was carried out. Pre-treatment of the animals with either theanine or minocycline showed no significant effects on the generation of the radical species or of the endogenous antioxidant which ruled out these as a mechanism of neuroprotection of both drugs, post-ischaemia.The findings of this study provide novel information on the possible mechanisms by which both theanine and minocycline act to bring about neuroprotection. In particular in this study, pre-treatment with minocycline has shown promise in the focal ischaemic model of stroke.

The use of minocycline for the treatment of a broad range of systemic infections and for severe acne has been associated with vestibular side effects. The severity of side effects may lead to poor adherence to therapy by patients. The use of sustained release formulations of minocycline that display slow dissolution of minocycline following administration may be beneficial in reducing the incidence and severity of side effects. Therefore, sustained release capsule dosage forms containing 100 mg minocycline (base) were manufactured and assessed for use as sustained release oral dosage forms of minocycline. Minocycline sustained release capsules were manufactured based on matrix technologies using hydroxypropylmethyl cellulose (HPMC) and Compritol® as release retarding polymers. The rate and extent of minocycline release from the capsules was evaluated using USP Apparatus 1 and samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection. Differences in the rate and extent of minocycline release from formulations manufactured using HPMC or Compritol® were influenced by the concentration of polymer used in the formulations. The rate and extent of minocycline release was faster and greater when low concentrations of polymer were used in formulations. The effect of different excipients on the release pattern(s) of minocycline and particularly their potential to optimise minocycline release from experimental formulations was investigated. The use of diluents such as lactose and microcrystalline cellulose (MCC) revealed that lactose facilitated minocycline release when HPMC was used as the polymer matrix. In contrast, the use of lactose as diluent resulted in slower release of minocycline from Compritol® based formulations. The addition of sodium starch glycolate to HPMC based formulations resulted in slower release of minocycline than when no sodium starch glycolate was used. Compritol® based formulations were observed to release minocycline faster following addition of sodium starch glycolate and Poloxamer 188 to experimental formulations. In vitro dissolution profiles were compared to a target or reference profile using the difference and similarity factors, ƒ1 and ƒ2 , and a one way analysis of variance (ANOVA). In addition, the mechanism of minocycline release was elucidated following fitting of dissolution data to the Korsmeyer-Peppas, Higuchi and Zero order models. Minocycline release kinetics were best described by the Korsmeyer-Peppas model and the values of the release exponent, n (italics), revealed that drug release was a result of the combined effects of minocycline diffusion through matrices and erosion of the matrices. These in vitro dissolution profiles were better fit to the Higuchi model than to the Zero order model. Two formulations that displayed a fit to the Zero order model were identified for further studies as potential dosage forms for sustained release minocycline.

The present study attempted to predict the serious side effects of akathisia and parkinsonism on the basis of individualized measurement of changes in visuomotor functioning. The following were the hypotheses for this investigation. 1. A deterioration of visuomotor ability as measured by a modification of Haase and Janssen' s (1965) Handwriting Test will predict which patients undergoing neuroleptic therapy will experience the extrapyramidal symptoms of akathisia and parkinsonism (symptom group) and which will not (no-symptom group). 2. A deterioration of visuomotor ability as measured by the Bender-Gestalt will predict which patients undergoing neuroleptic therapy will experience the extrapyramidal symptoms of akathisia and parkinsonism (symptom group) and which will not (no-symptom group). It was not possible to predict the symptom group as a whole on the basis of the Handwriting Test scores since a t test of the difference was not significant between group means. However, inspection of these scores showed clear deterioration of performance among the patients who experienced parkinsonian reactions as opposed to those who experienced akathisia or who did not experience extrapyramidal symptoms at all. The symptom group was separated into akathisic and parkinsonian groups and compared to the subjects who did not experience extrapyramidal side effects (no-symptom group). A one-way ANOVA showed a nonsignificant difference between the three groups. Similar analysis of the Bender-Gestalt scores failed to support the second hypothesis since no significant difference was found between groups.

Made available in DSpace on 2015-09-17T15:26:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-05-04. Added 1 bitstream(s) on 2015-09-17T15:45:57Z : No. of bitstreams: 1 000842358_20160501.pdf: 688314 bytes, checksum: c0e58d7c09371b47da4b8dfd21b13c6b (MD5) Bitstreams deleted on 2016-05-04T13:08:28Z: 000842358_20160501.pdf,. Added 1 bitstream(s) on 2016-05-04T13:09:32Z : No. of bitstreams: 1 000842358.pdf: 2362291 bytes, checksum: 607ef5f590e4380cff19bf4d439fa958 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introdução. O omeprazol é amplamente administrado e, na maioria das vezes, o uso é efetivo e seguro. No entanto, estudos avaliaram que o omeprazol foi o medicamento mais relacionado com a admissão hospitalar devido RAM. Tais RAM talvez possam ser explicadas devido ao uso abusivo ou prescrição irracional de omeprazol. Todavia, não foi avaliado o risco e o benefício do uso profilático do omeprazol, considerando o uso aprovado e o uso não aprovado, e as consequências para a segurança do paciente. Objetivo. Identificar e avaliar o risco de ocorrência de EAM e o benefício através da efetividade do uso profilático de omeprazol em pacientes internados. Método. Conduziu-se um estudo coorte observacional de agosto a outubro de 2013 e dezembro/2013 a maio/2014, no Hospital Estadual Américo Brasiliense. Os pacientes internados foram classificados em três grupos: a) uso de omeprazol profilático aprovado, b) uso de omeprazol profilático não aprovado; c) não uso de omeprazol. Foram excluídos os pacientes que fizeram uso de omeprazol não profilático. Os pacientes foram monitorados diariamente com auxílio do roteiro de investigação adequado previamente. Os dados foram tabulados segundo a presença ou ausência de efetividade e de eventos adversos nos três grupos. Resultados. Foram monitoradas 427 hospitalizações, sendo 136 expostos ao omeprazol profilático não aprovado e 52 expostos ao omeprazol profilático aprovado. Identificaram-se apenas dois casos de suspeita de inefetividade e 14 de eventos adversos. Observou-se diferença significativa na concentração sérica da creatinina e ureia para os pacientes que usavam omeprazol profilático aprovado. Conclusão. Há duas vezes mais pacientes expostos ao omeprazol profilático não aprovado comparado ao uso aprovado. Não houve associação do omeprazol profilático com fator de risco, no entanto, houve diferença significativa no... / Introduction. Omeprazole is a widely used drug; in most cases, it is effective and safe. However, studies have found omeprazole to be the drug most frequently related to hospital admissions due to adverse drug reactions (ADRs). The ADRs could have occurred as a result of abuse or irrational prescribing of omeprazole. Despite that possibility, the risks and benefits of prophylactic omeprazole considering the approved and off-label uses and the potential consequences for patient safety have not been assessed. Objective. To identify and assess the risk of adverse drug events and the benefit provided by the effective use of prophylactic omeprazole in hospitalized patients. Methods. This observational cohort study was conducted from August to October 2013 and December 2013 to May 2014 at the Américo Brasiliense State Hospital. The inpatients were classified into three groups: a) approved use of prophylactic omeprazole b) off-label use of prophylactic omeprazole, and c) not using omeprazole. Patients who used no prophylactic omeprazole were excluded. The patients were monitored daily with the aid of a pre-established research protocol. Data were tabulated according to drug effectiveness or ineffectiveness and presence of adverse events in the three groups. Results. A total of 427 hospitalized patients were monitored in the study. Of these, 136 patients were exposed to prophylactic omeprazole used off-label and 52 exposed to on-label use of prophylactic omeprazole. Two cases of suspected ineffectiveness and 14 adverse events were recorded. There was a significant difference in serum creatinine and urea for patients using on-label prophylactic omeprazole. Conclusion. There are twice as many patients using off-label prophylactic omeprazole as patients using it for approved indications. There was no association of prophylactic omeprazole with risk factors, but there was a significant difference in the increase in serum creatinine and urea for ... / FAPESP: 13/12681-2