PIPc study: development of indicators of potentially inappropriate prescribing in children (PIPc) in primary care using a modified Delphi technique

Objective There is limited evidence regarding the quality of prescribing for children in primary care. Several prescribing criteria (indicators) have been developed to assess the appropriateness of prescribing in older and middle-aged adults but few are relevant to children. The objective of this study was to develop a set of prescribing indicators that can be applied to prescribing or dispensing data sets to determine the prevalence of potentially inappropriate prescribing in children (PIPc) in primary care settings.


Design Two-round modified Delphi consensus method.


Setting Irish and UK general practice.


Participants A project steering group consisting of academic and clinical general practitioners (GPs) and pharmacists was formed to develop a list of indicators from literature review and clinical expertise. 15 experts consisting of GPs, pharmacists and paediatricians from the Republic of Ireland and the UK formed the Delphi panel.


Results 47 indicators were reviewed by the project steering group and 16 were presented to the Delphi panel. In the first round of this exercise, consensus was achieved on nine of these indicators. Of the remaining seven indicators, two were removed following review of expert panel comments and discussion of the project steering group. The second round of the Delphi process focused on the remaining five indicators, which were amended based on first round feedback. Three indicators were accepted following the second round of the Delphi process and the remaining two indicators were removed. The final list consisted of 12 indicators categorised by respiratory system (n=6), gastrointestinal system (n=2), neurological system (n=2) and dermatological system (n=2).


Conclusions The PIPc indicators are a set of prescribing criteria developed for use in children in primary care in the absence of clinical information. The utility of these criteria will be tested in further studies using prescribing databases.

Síndrome de Sjögren Primário

A Síndrome de Sjögren (SS) é uma das três patologias autoimunes mais frequentes na população mundial, ainda assim frequentemente infradiagnosticada. Esta síndrome é uma doença autoimune crónica que afeta as glândulas exócrinas, particularmente as glândulas salivares e lacrimais. A SS primária (SSp) afeta especificamente as glândulas exócrinas, enquanto que a SS secundária (SSs) aparece associada a outras patologias autoimunes sistémicas. A SS é caracterizada, histopatologicamente, por um infiltrado inflamatório linfocitário que interfere com a função glandular normal. Afeta 0,5% da população mundial, sendo claramente mais predominante em mulheres (9:1 versus homens), principalmente por volta dos 50 anos (após a menopausa), ainda que também possa aparecer depois da menarca (entre os 20 e os 30 anos). Considera se que a etiologia da SS é multifatorial. Fatores genéticos, ambientais, hormonais e virais estão implicados na sua etiopatogénese. É muito importante o papel dos Médicos Dentistas no diagnóstico da SSp, uma vez que na maior parte dos casos são eles quem detetam os primeiros sintomas, mais propriamente a boca seca. Diversos testes auxiliares são utilizados para o diagnóstico desta doença, tais como: o teste de Schimer, o teste de Rosa Bengala, a Sialometria, a Sialografia, a Biópsia das glândulas salivares, entre outros. A SSp, regra geral, tem um curso não doloroso, sendo a boca seca e a secura ocular as suas duas características clínicas mais salientes. A maior parte das manifestações orais que se apresentam nestes pacientes são resultado de hipofunção das glândulas salivares (da boca seca), tais como: a cárie dentária, a doença periodontal, as infeções fúngicas, entre outras. Esta doença também se pode associar a problemas a nível sistémico, que podem ser subdivididos em não viscerais (pele, artralgia, mialgia) e viscerais (pulmão, coração, rim, sistema gastrointestinal, sistema endócrino e sistema nervoso central e periférico). O tratamento é empírico, sintomático e direcionado a tratar as complicações da doença mais inicial, que consiste em limitar os danos da xerostomia e da queratoconjuntivite. A prevenção dos sintomas a nível oral e ocular é fundamental em pacientes com SSp, para assim terem maior qualidade de vida.

Chylous Ascites in Systemic Lupus Erythematosus (SLE) Patients

The gastrointestinal system is commonly implicated in Systemic Lupus Erythematosus (SLE). Ascites, produced by several mechanisms has been reported as a systemic manifestation of lupus, but only rarely as an initial presentation of the disease. Its appearance is often insidious and without abdominal pain. Chylous ascites (such as chyle in the peritoneal cavity) has seldom been reported in SLE. We describe a case of chylous ascites in an SLE patient, reviewing the other published cases, its pathophysiology and its management.

Knowledge about sources of dietary fibres and health effects using a validated scale: a cross-country study

Objectives Dietary fibre (DF) is one of the components of diet that strongly contributes to health improvements, particularly on the gastrointestinal system. Hence, this work intended to evaluate the relations between some sociodemographic variables such as age, gender, level of education, living environment or country on the levels of knowledge about dietary fibre (KADF), its sources and its effects on human health, using a validated scale. Study design The present study was a cross-sectional study. Methods A methodological study was conducted with 6010 participants, residing in 10 countries from different continents (Europe, America, Africa). The instrument was a questionnaire of self-response, aimed at collecting information on knowledge about food fibres. The instrument was used to validate a scale (KADF) which model was used in the present work to identify the best predictors of knowledge. The statistical tools used were as follows: basic descriptive statistics, decision trees, inferential analysis (t-test for independent samples with Levene test and one-way ANOVA with multiple comparisons post hoc tests). Results The results showed that the best predictor for the three types of knowledge evaluated (about DF, about its sources and about its effects on human health) was always the country, meaning that the social, cultural and/or political conditions greatly determine the level of knowledge. On the other hand, the tests also showed that statistically significant differences were encountered regarding the three types of knowledge for all sociodemographic variables evaluated: age, gender, level of education, living environment and country. Conclusions The results showed that to improve the level of knowledge the actions planned should not be delineated in general as to reach all sectors of the populations, and that in addressing different people, different methodologies must be designed so as to provide an effective health education.

Saccharomyces Boulardii in Helicobacter Pylori Eradication in Children: A Randomized Trial From Iran

Background: Helicobacter Pylori infects around 50% of the human population and is asymptomatic in 70% of the cases. H.pylori eradication in childhood will not only result in peptic symptoms relief, but will also prevent late-term complications such as cancer. Today, probiotics are being increasingly studied in the treatment of gastrointestinal infections as an alternative or complement to antibiotics. Objectives: In this study we aimed to assess the effect of S. boulardii supplementation on H.pylori eradication among children in our region. Patients and Methods: In this randomized double-blind placebo-controlled clinical trial 28 asymptomatic primary school children with a positive H.pylori stool antigen (HpSA) exam were randomly allocated into the study group, receiving Saccharomyces Boulardii and the control group receiving placebo capsules matched by shape and size, for one month. The children were followed up weekly and were reinvestigated four to eight weeks after accomplished treatment by HpSA testing. The significance level was set at P < 0.05. Results: 24 children completed the study. The mean HpSA reduced from 0.40 ± 0.32 to 0.21 ± 0.27 in the study group, indicating a significant difference (P = 0.005). However, such difference was not observed in the control group (P = 0.89). Moreover, the HpSA titer showed a 0.019 ± 0.19 decrease in the study group whereas the same value was 0.0048 ± 0.12 for the controls, again stating a significant difference (P = 0.01). Conclusions: Saccharomyces boulardii has a positive effect on reducing the colonization of H.pylori in the human gastrointestinal system but is not capable of its eradication when used as single therapy.

A decision support system to facilitate management of patients with acute gastrointestinal bleeding

Objective: To develop a model to predict the bleeding source and identify the cohort amongst patients with acute gastrointestinal bleeding (GIB) who require urgent intervention, including endoscopy. Patients with acute GIB, an unpredictable event, are most commonly evaluated and managed by non-gastroenterologists. Rapid and consistently reliable risk stratification of patients with acute GIB for urgent endoscopy may potentially improve outcomes amongst such patients by targeting scarce health-care resources to those who need it the most. Design and methods: Using ICD-9 codes for acute GIB, 189 patients with acute GIB and all. available data variables required to develop and test models were identified from a hospital medical records database. Data on 122 patients was utilized for development of the model and on 67 patients utilized to perform comparative analysis of the models. Clinical data such as presenting signs and symptoms, demographic data, presence of co-morbidities, laboratory data and corresponding endoscopic diagnosis and outcomes were collected. Clinical data and endoscopic diagnosis collected for each patient was utilized to retrospectively ascertain optimal management for each patient. Clinical presentations and corresponding treatment was utilized as training examples. Eight mathematical models including artificial neural network (ANN), support vector machine (SVM), k-nearest neighbor, linear discriminant analysis (LDA), shrunken centroid (SC), random forest (RF), logistic regression, and boosting were trained and tested. The performance of these models was compared using standard statistical analysis and ROC curves. Results: Overall the random forest model best predicted the source, need for resuscitation, and disposition with accuracies of approximately 80% or higher (accuracy for endoscopy was greater than 75%). The area under ROC curve for RF was greater than 0.85, indicating excellent performance by the random forest model Conclusion: While most mathematical models are effective as a decision support system for evaluation and management of patients with acute GIB, in our testing, the RF model consistently demonstrated the best performance. Amongst patients presenting with acute GIB, mathematical models may facilitate the identification of the source of GIB, need for intervention and allow optimization of care and healthcare resource allocation; these however require further validation. (c) 2007 Elsevier B.V. All rights reserved.

In vivo and in vitro studies on the expression and function of TFF peptides in the gastrointestinal tract and the central nervous system

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2014

AC Biosusceptometry as a Tool for Monitoring the Gastrointestinal Transit of Multiparticulate Drug Delivery System

Drug delivery systems based on natural polysaccharides, such as chitosan (CS) and pectin (PC), rather than on synthetic polymers, have been widely studied. Some reasons for that are low toxicity and costs and high biodegradability of the formers. A multiparticulate system based on CS and PC was developed in our laboratories, including the addition of an enteric polymer, cellulose acetate phtalate (CAP). Such improvement promoted stronger gastric and enteric resistances, as assessed in vitro, making the systems more selective to enzymatic degradation in the colon. Although in vitro dissolution tests can simulate some properties concerning the gastrointestinal transit (GT), collaborating to characterize the systems behavior in the biological fluids, frequently they do not result in satisfactory in vitro/in vivo correlations. The objective of this work was to follow in vivo the GT of the particles developed by means of AC biosusceptometry (ACB), a non-invasive and of low cost methodology. The particles containing ferrite in powder form were prepared by complex coacervation using an ideal 3:1:1 mass ratio for PC:CS:CAP. The magnetic particles were administered to healthy volunteers by oral route. The GT was monitored by using multi-sensor ACB system and the signal acquisition was performed every IS min until the colonic region was reached. By means of ACB technique, it was possible to acquiring images generated by the magnetic particles within the whole gastrointestinal tract including the colonic region. Variable particles transit times were observed among the volunteers, but without interference on the mapping of the particles until the colonic region. The particles were able to produce magnetic field strong enough to generate signals adequate for mapping the particles. The results suggest that integral particles reached the colon, after they resisted against gastric and enteric media. Studies associating transit time and in vivo drug release are in development in order to confirm the efficiency of the systems.

Gastrointestinal helminths in calves and cows in an organic milk production system

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Gastrointestinal parasites occurrence in dairy cows kept in organic and conventional production system

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The mucosal immune system at the gastrointestinal barrier

The immune system faces a considerable challenge in its efforts to maintain tissue homeostasis in the intestinal mucosa. It is constantly confronted with a large array of antigens, and has to prevent the dissemination and proliferation of potentially harmful agents while sparing the vital structures of the intestine from immune-mediated destruction. Complex interactions between the highly adapted effector cells and mechanisms of the innate and adaptive immune system generally prevent the luminal microflora from penetrating the intestinal mucosa and from spreading systemically. Non-haematopoietic cells critically contribute to the maintenance of local tissue homeostasis in an antigen-rich environment by producing protective factors (e.g. production of mucus by goblet cells, or secretion of microbicidal defensins by Paneth cells) and also through interactions with the adaptive and innate immune system (such as the production of chemotactic factors that lead to the selective recruitment of immune cell subsets). The complexity of the regulatory mechanisms that control the local immune response to luminal antigens is also reflected in the observation that mutations in immunologically relevant genes often lead to the development of uncontrolled inflammatory reactions in the microbially colonized intestine of experimental animals.

Parkinson's disease and gastrointestinal dysfunctions: morphological, neurochemical and functional modifications of the enteric nervous system associated with central dopaminergic impairment

Parkinson’s disease (PD) is frequently associated with gastrointestinal (GI) symptoms, mostly represented by abdominal distension, constipation and defecatory dysfunctions. Despite GI dysfunctions have a major impact on the clinical picture of PD, there is currently a lack of information on the neurochemical, pathological and functional correlates of GI dysmotility associated with PD. Moreover, there is a need of effective and safe pharmacological therapies for managing GI disturbances in PD patients. The present research project has been undertaken to investigate the relationships between PD and related GI dysfunctions by means of investigations in an animal model of PD induced by intranigral injection of 6-hydroxydopamine (6-OHDA). The use of the 6-OHDA experimental model of PD in the present program has allowed to pursue the following goals: 1) to examine the impact of central dopaminergic denervation on colonic excitatory cholinergic and tachykininergic neuromotility by means of molecular, histomorphologic and functional approaches; 2) to elucidate the role of gut inflammation in the onset and progression of colonic dysmotility associated with PD, characterizing the degree of inflammation and oxidative damage in colonic tissues, as well as identifying the immune cells involved in the production of pro-inflammatory cytokines in the gut; 3) to evaluate the impact of chronic treatment with L-DOPA plus benserazide on colonic neuromuscular activity both in control and PD animals. The results suggest that central nigrostriatal dopaminergic denervation is associated with an impaired excitatory cholinergic neurotransmission and an enhanced tachykininergic control, resulting in a dysregulated smooth muscle motor activity, which likely contributes to the concomitant decrease in colonic transit rate. These motor alterations might result from the occurrence of a condition of gut inflammation associated with central intranigral denervation. The treatment with L-DOPA/BE following central dopaminergic neurodegeneration can restore colonic motility, likely through a normalization of the cholinergic enteric neurotransmission, and it can also improve the colonic inflammation associated with central dopaminergic denervation.

Design, synthesis and evaluation of dipeptides as probes for studies of gastrointestinal tract dipeptide transport system

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Intrinsic Dissolution as a Tool for Evaluating Drug Solubility in Accordance with the Biopharmaceutics Classification System

The Biopharmaceutics Classification System (BCS) is a tool that was created to categorize drugs into different groups according to their solubility and permeability characteristics. Through a combination of these factors and physiological parameters, it is possible to understand the absorption behavior of a drug in the gastrointestinal tract, thus contributing to cost and time reductions in drug development, as well as reducing exposure of human subjects during in vivo trials. Solubility is attained by determining the equilibrium under conditions of physiological pH, while different methods may be employed for evaluating permeability. On the other hand, the intrinsic dissolution rate (IDR), which is defined as the rate of dissolution of a pure substance under constant temperature, pH, and surface area conditions, among others, may present greater correlation to the in vivo dissolution dynamic than the solubility test. The purpose of this work is to discuss the intrinsic dissolution test as a tool for determining the solubility of drugs within the scope of the Biopharmaceutics Classification System (BCS).