1,721,018 research outputs found
The reason for failure of on-demand PPI therapy in NERD patients.
No full textTo The Editors:
We read with interest the paper by Wu et al (1) showing that concomitant irritable bowel syndrome, in addition to functional dyspepsia, is associated with failure of on-demand Proton Pump Inhibitors (PPI) therapy in reflux patients. The Authors performed a large study in which all patients underwent conventional manometry and pH monitoring in order to be characterized. They included in the group with non-erosive reflux disease (NERD) patients with abnormal acid exposure and those with normal acid and a strong correlation between symptoms and acid reflux events (SI>75%). They classified patients with negative symptoms association as having functional heartburn (FH) and excluded them from the study.
The separation of FH from NERD represents a very important point, because the former sub-group is likely to be associated more frequently with other functional GI disorders and this can influence the therapeutic PPIs response. Indeed, in a recent study (2), we have shown that sub-grouping the complex population of endoscopy-negative reflux patients by means of impedance-pH testing led us to demonstrate that several dyspeptic symptoms, such as those pertaining to the postprandial distress syndrome (3), overlap significantly more with FH than with NERD. This sustains the concept that FH may be part of functional GI disorders, in which other factors (i.e. visceral hypersensitivity, psychological factors, etc.) rather than acid seem to play a major role. Therefore, the response to PPI therapy, given in whatever modality in these patients, is very poor.
However, the fact that NERD patients had higher failure rate of on-demand PPI therapy than those with Erosive Esophagitis (EE), even after Wu et al had excluded FH from their study, may depend on additional factors. For instance, the use of traditional pH-metry alone allowed the Authors to detect only NERD patients with an esophagus hypersensitive to acid, while those with a positive symptom association with weakly acidic reflux were necessarily missed. The modern impedance-pH technique has the merit to distinguish acid from weakly acidic reflux events and this allowed us to demonstrate that there is a subgroup of endoscopy-negative patients who have a clear association between heartburn and weakly acidic reflux episodes (4). The presence of patients pertaining to this last subgroup among those with NERD and normal acid in their esophagus represents one of the main causes of non response to PPIs (5) and could explain why in the above study the failure rate to these drugs was higher in NERD than in EE
The relevance of reflux monitoring off therapy.
No full textTo The Editors:
We read the recent article by Vaezi MF. (1) with interest. The Author discussed on the opportunity to evaluate patients with symptoms suggestive of gastro-oesophageal reflux (GERD) by means of 24-h pH or impedance-pH monitoring On or Off therapy. He concluded that, after an empiric trial with twice-daily PPI therapy, in case of refractoriness, patients should undergo reflux monitoring On therapy in order to exclude reflux disease, while testing Off therapy has a limited value, because in this group it results only in an additional test proving what is already established by patients’ lack of response to aggressive PPI therapy.
We agree that an empiric treatment with a twice daily PPI trial is the correct initial approach to patients with suspected GERD and testing should be reserved only to those with persisting symptoms despite antisecretory drugs. However, we believe that a particular attention must be taken when considering the endoscopy-negative population. We have recently observed that patients with non-erosive reflux disease (NERD) evaluated using impedance-pH monitoring Off therapy (2) have frequently symptoms related to weakly acidic reflux, mainly in case of normal esophageal acid exposure. This appears a relevant point, in that we are now able to subtract this subgroup of patients with weakly acidic reflux disease from those without any reflux underlying their symptoms (functional heartburn, FH). These two subgroups require completely different therapeutic approaches (surgery or pain-modulators), although limited outcome data are available in this field (3,4). On the other hand, a recent study (4) has shown that NERD patients refractory to PPIs can equally respond to surgery. In the endoscopy-negative population the risk of including FH in NERD is rather high and we have shown that PPI therapy may cause an underestimation of GERD patients (inability to identify weakly acidic reflux patients) and an overestimation of FH patients (placebo effect) (5). These findings have been confirmed in a recent investigation, in which the analysis of PPIs response in a large number of endoscopy-negative patients with heartburn revealed that those patients with normal acid exposure and positive symptom association had a 50% response to PPIs (6). Therefore, we confirmed that the negative response to PPI therapy does not mean immediately that reflux can be excluded.
Overall, in our opinion, impedance-pH testing On therapy is more indicated in patients with proven reflux disease (erosive esophagitis, Barrett’s esophagus, previous abnormal pH-metry), while endoscopy-negative patients not responding to PPIs should be better assessed Off antisecretory therapy in order to be sure that they have GERD or not
Nocturnal reflux and sleep disturbances: an overlooked link in the past.
No full textCommentary
Gastro-oesophageal reflux disease (GORD) is highly prevalent in western countries. The main clinical manifestations are represented by heartburn and regurgitation and they are commonly used for the diagnosis of GORD, although their accuracy is far from optimal (1). The above symptoms can occur during the daytime and also throughout the nocturnal period. In the past, the progressively widespread use of 24-hour oesophageal pH-metry showed that the majority of reflux events belong to the post-prandial periods, while they are much less frequent during the nighttime (2). This temporal distribution of abnormal reflux episodes provided the rationale to explain, at least in part, the benefit of proton pump inhibitors (PPIs) in patients with GORD. In fact, these drugs are more effective during the daytime, when proton pumps are activated by fractioned meals, than through the nighttime, when their main pharmacological target does not work because of sleep (3). Despite the above findings, in the last decade we have witnessed a mounting evidence of the role of nighttime GORD in provoking a decreased quality of life, a variety of sleep disorders and diminished work performances (4). Several epidemiological surveys have confirmed that nocturnal reflux symptoms, in particular heartburn and regurgitation, can be reported by 2 out of 3 patients with GORD (5) and the relationship between GORD and sleep disorders has been recently established by many studies which have clearly demonstrated that 47%-57% of the GORD patients and approximately 25% of the US adult general population report having heartburn that awakens them from sleep during the night (6,7). Of the GORD patients, 63% report that they are unable to sleep well, 42% are unable to sleep during a full night, 39% have to take naps during the day and 34% have to sleep in a seated position because of nighttime heartburn (7). It has also been shown that sleep deprivation per se can adversely influence GORD, in that the inability to have a complete rest during the night is a potential mechanism for increasing the perception of symptoms in patients with GORD (8). Another important issue is the still poorly understood role of nocturnal reflux in determining extra-oesophageal and particularly respiratory symptoms because of the well-known longer-lasting duration and the slower clearing of supine refluxes compared with the daytime ones (9). Finally, the use of impedance-pH monitoring has shown that nocturnal weakly acidic reflux is as common as acid reflux in GORD patients (10) and a recent study has also proposed that this kind of nighttime reflux can sensitize oesophageal mucosa to the point to favor the occurrence of diurnal symptoms, such as sour or bitter taste in the mouth (11).
The observational study performed in this field by French researchers (12) represents a further confirmation of the relevance of nocturnal reflux symptoms in the genesis of sleep disturbances leading to a reduced quality of life and work productivity on the day after. The strengths of the study consist in the high number of involved primary care physicians and the great sample of patients with nighttime GORD recruited by them. Nocturnal reflux symptoms were reported by 63,9% of the patients they analyzed and regular sleep disorders by 61,7% of them. These rates are quite similar to those already registered in previous epidemiological studies on this matter in western countries (4-7).
In the study from Cadiot et al, multivariate statistical analysis demonstrated that nocturnal GORD symptoms, the age over 50 years and the use of hypnotic drugs were independent predictors of sleep disturbances. The last factor is of particular interest, because many doctors and patients ignore that drugs such as benzodiazepines, which are frequently taken by elderly people chronically and life-long, are associated with a slowing of gastric emptying and a reduction of lower oesophageal sphincter basal pressure, two of the main mechanisms favoring reflux events (8).
The French Authors also showed that the control of GORD by administration of PPI therapy provoked a substantial decrease of nocturnal symptoms from 98,8% to 39,3% in patients reporting at least one nocturnal GORD symptom during the previous week and this was associated with the considerable improvement of other features pertaining to sleep disturbances. This is an important outcome of medical therapy of nighttime GORD, although the persistence of symptoms in about 40% of patients treated for 1 month with PPI therapy is a confirmation of the difficulty in blocking completely nocturnal reflux by the most powerful anti-secretory drugs at present used to cure GORD. In fact, they are more effective during the daytime than the nighttime as result of the activation of proton pumps by meals, unless we give them as double fractioned daily doses (3) or before dinner instead of before breakfast (13). Unfortunately, however, there is no mention of the dosing of PPIs, which were taken by almost all patients evaluated by Cadiot et al in their study.
It must be acknowledged that the French investigation has other important limitations. Firstly, it has not been described whether the questionnaire the Authors used to collect symptom data was previously validated or was one of those already adopted for similar studies in the same field. It is well known that many of the questionnaires aimed at collecting subjective variables, such as symptoms, are questionable (14) and this is particularly true when changes of symptoms over time are monitored, as it was done before and one month after drug intake in patients with nocturnal symptoms who were recruited by the physicians coordinated by Cadiot et al. Secondly, PPI therapy was not only poorly defined in terms of dosage and timing of intake, but it is also evident that it was administered in uncontrolled manner. This represents a relevant bias in the interpretation of the results they obtained, even though the Authors themselves recognize that it would have been very difficult to organize a randomized, controlled trial in relation of the complex setting of the study. Thirdly, nocturnal cough cannot be considered with certainty as a reflux symptom, because it can be due to many causes and therefore needs to be substantiated by the use of more objective measurements. On the other hand, also typical reflux symptoms were defined in the study as GORD–related exclusively on the basis of patients’ perception and a more sound way to establish this relationship was lacking. Once again, this limitation is clearly due to large scale observational studies, which do not allow us to use more rigorous methods to show a firm link between symptoms and reflux events.
In conclusion, this French research adds new fuel to the clinical relevance of an overlooked feature of reflux disease in the past, that is the important role of nocturnal reflux in inducing sleep disturbances and reduced work productivity on the day after. It is likely that we have to address more attention to nighttime GORD and to find additional drugs which are able to control it better than PPIs, which represent the first choice anti-reflux therapy today available. However, if the relationship between nocturnal reflux and sleep disturbances is established with great accuracy on the basis of instrumental methods, it is likely that patients with poor response to medical treatment can benefit from surgical fundoplication as further therapeutic option, even though data on the impact of this intervention on the improvement of sleep parameters related to nighttime reflux are very limited
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Comment to "current applications of evolving methodologies in gastroesophageal reflux disease testing".
No full textTo The Editor:
We read with great interest the review article by Weber et al (1) on current applications of new methodologies in gastroesophageal reflux testing. The Authors assessed almost all the available literature published in this field after the advent of wireless capsule pH and impedance-pH monitoring and discussed the clinical applicability, advantages and limits of these new techniques. In particular, they reported that the major advantage of impedance-pH testing relies in the detection of weakly acidic reflux (WAR), that allows clinicians to identify more patients whose reflux is responsible for their symptoms and quoted several investigations, mainly performed in Gastro-oesophageal Reflux Disease (GORD) patients without endoscopic assessment, in order to support their conclusions (2). However, we believe that the above studies do not represent adequately the entire knowledge we have accumulated in last years on the relevance of impedance-pH in GORD patients.
If it is true that the importance of MII-pH testing relies more on establishing the symptom association with both acid and weakly acidic reflux events than on quantifying reflux episodes, it must be underlined that this advantage becomes more and more relevant when evaluating patients with clear evidence of no mucosal breaks at upper endoscopy (Non-Erosive Reflux Disease = NERD) rather than the overall population with GORD (3,4). This appears more relevant if we consider that NERD represents the most frequent phenotypic presentation of GORD, amounting to 60%-70% of overall reflux patients. Indeed, in a recent investigation by our group (3), a series of 150 NERD patients off acid suppressive medication were studied by means of MII-pH and we found that 17% of them presented reflux symptoms associated with WAR alone or combined with acid reflux, despite a normal esophageal acid exposure. The identification of this subgroup of NERD patients whose symptoms were clearly related to WAR is a new finding due to MII-pH and contributes to enlarge substantially the group of NERD with an oesophagus hypersensitive not only to acid but also to WAR (this global subset amounts to 37% in our study). Moreover, it must be stressed that the identification of this new subgroup has also the merit to narrow down the proportion of endoscopy-negative patients who do not have any kind of reflux underlying their symptoms and who may be classified as having functional heartburn (FH) , as also confirmed by a recent investigation assessing the added value of impedance-pH testing to Rome III criteria in distinguishing FH from NERD (5). Also the evidence that patients with FH identified by means of impedance-pH testing presents more frequently functional dyspepsia (FD) than the other subsets supports the concept that impedance testing is able to differentiate NERD from FH patients (4).
In conclusion, we believe that all the above features have contributed to improve our knowledge of the complex pathophysiology of GORD, and represent an important step favouring the knowledge and management of endoscopy-negative reflux patients. This has been obtained exclusively by the wide application of impedance-pH in daily clinical practice. We believe that the Authors of the review would have mentioned this important pathophysiological and clinical progress which is one the major results of the new technique
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