Laryngopharyngeal reflux: A confounding cause of aerodigestive dysfunction.

BACKGROUND: Laryngopharyngeal reflux (LPR) is one of the most common and important disorders of upper airway inflammation. It causes significant impairment to quality of life, and can predict serious laryngeal and oesophageal pathology, yet it remains under-diagnosed and under-treated. OBJECTIVE: This paper attempts to unravel the diagnostic dilemma of LPR and provide a practical, discriminating approach to managing this common condition. DISCUSSION: Historical red flags mandating early referral for specialist review are identified, and pathophysiology, symptomatology and common signs are reviewed. In addition, a comprehensive treatment plan consisting of lifestyle modifications, counselling aids and empirical medical therapy is proposed. A strategy for tracking clinical improvement using Belfasky's validated symptom index is included to aid counselling, compliance and follow-up.

Optogenetic inhibition of cocaine seeking in rats.

Inhibitory optogenetics was used to examine the roles of the prelimbic cortex (PL), the nucleus accumbens core (NAcore) and the PL projections to the NAcore in the reinstatement of cocaine seeking. Rats were microinjected into the PL or NAcore with an adeno-associated virus containing halorhodopsin or archaerhodopsin. After 12 days of cocaine self-administration, followed by extinction training, animals underwent reinstatement testing along with the presence/absence of optically induced inhibition via laser light. Bilateral optical inhibition of the PL, NAcore or the PL fibers in the NAcore inhibited the reinstatement of cocaine seeking.

Seguridad e interacciones de los IBP / Security and interactions of PPIs

Los IBP han demostrado ser fármacos relativamente seguros después de muchos años de una amplia utilización. Las reacciones adversas con las que más frecuentemente se han asociado son leves y con escasa repercusión clínica. Inducen hipergastrinemia pero esta no se ha relacionado con una capacidad para inducir lesiones malignas Parece que pueden facilitar determinadas infecciones bacterianas a nivel digestivo y del aparato respiratorio, aunque este hecho no limita su prescripción dada la facilidad de su tratamiento. Desde el punto de vista farmacocinético se han descrito la posibilidad de interacciones con otros fármacos a nivel del citocromo P450, pero ello no parece tener mayor trascendencia clínica y terapéutica en general. Sin embargo, recientemente se está incidiendo por las agencias reguladoras en la hipotética interacción de los IBP (sobre todo omeprazol) con el clopidogrel generando una reducción en su efecto antiagregante. Aunque se debe seguir esta recomendación, necesitaria ser evaluado de forma específica para poder determinar su realidad clínica y las posibles alternativas existentes en los pacientes con riesgo de sangrado gastrointestinal. En último lugar se revisa su administración en situaciones especiales, objeto de discusión, como en la mujer embarazada o durante la lactancia materna...

Application of lag-time into exposure definitions to control for protopathic bias.

PURPOSE: To control for protopathic bias, some studies have incorporated the concept of lag-time into their exposure definition (time period before the index date that was not considered in assessing exposure). The objective of this study was to introduce a procedure to identify the best lag-time to be applied in studies where control for protopathic bias is required. METHODS: We used data from a case-control study carried out to assess the association between exposure to proton pump inhibitors (PPIs) and risk of gastric cancer, using RAMQ databases. Exposure was defined as the number of defined daily doses of PPIs dispensed during the 5-year period prior to the index date (divided into four quartiles). Thirty-one different lag-times were applied (0-30 months) based on 1-month intervals. Logistic regression was used to estimate the matched odds ratio (OR) for each lag-time. The change point in the ln(ORs) was identified by applying a two-compartmental model and a segmented regression model. RESULTS: A trend of decreasing ORs was found with the application of an increasing lag-time. As an illustration, the ORs for the 1st quartile of defined daily doses, when applying the 31 different lag-times, ranged between 3.52 when applying a 0 lag-time and 0.97 when applying a 30 months lag-time. Applying the two methods for the different lag-times showed that the ORs stabilized at around 6 months. CONCLUSION: For the purpose of controlling for protopathic bias in pharmacoepidemiological studies, we have provided a method to assess the most appropriate lag-time that should be applied for the assessment of drug exposure.

Atypical symptoms of GORD in Belgium: epidemiological features, current management and open label treatment with 40 mg esomeprazole for one month.

UNLABELLED: Frequency of atypical symptoms in patients suffering from gastro-oesophageal reflux disease (GORD) is not well known, and the optimal management of such symptoms has not been well established. Our aims were to set up an observatory of these atypical symptoms of GORD in Belgium and to study the efficacy of one month treatment with esomeprazole 40 mg. PATIENTS AND METHODS: Gastroenterologists participating in this observational survey were asked to register every new outpatient with symptoms of GORD during a period of 20 consecutive working days. All patients who reported predominant presence of atypical manifestations of GORD were documented and characterized more in detail. In patients with dominant chest pain or ENT symptoms, a treatment with esomeprazole 40 mg daily during 4 weeks was proposed. RESULTS: 90 gastroenterologists included 2864 patients consulting for symptoms suggestive of GORD, including 776 (27.1%) with dominant atypical symptoms. Endoscopy (performed in 2800 patients) showed significantly less oesophagitis in atypical than in typical GORD patients (68% vs. 81.1%; P < 0.0001). Management of atypical GORD patients appeared to be very heterogeneous. Overall 516/776 patients were included in the open phase of treatment with esomeprazole 40 mg, but data for analysis are only available in 228 patients. After one month, symptoms had disappeared in 57.1% and significantly improved in 26.6%. CONCLUSION: Atypical GORD represents a large number of consultations in gastroenterology in Belgium. It is associated with less endoscopic lesions than typical GORD. Its management is heterogeneous reflecting the lack of guidelines on this topic. Response rate after esomeprazole 40 mg for one month in this open uncontrolled trial was high. This result warrants confirmation in a placebo-controlled trial.

[Helicobacter pylori infection as a cause of sideropenic anaemia resistant to treatment - own observation]. / Zakazenie Helicobater pyroli przyczna niedokrwistosci niedobarwliwej opornej na leczenie- obserwacje wlasne.

A relationship is described between H. pylori infection and diseases localized beyond the gastrointestinal tract, for example: atherosclerosis, stenocardia, cerebral stroke, chronic urticaria, rosacea, hemicrania and in, children with height deficit or anaemia, caused by iron deficiency. Two cases of sideropenic anaemia in children resistant to oral iron are presented. Gastrointestinal tract symptoms were not observed and most probably the reason for anaemia was H. pylori infection. The first 14 years old patient with normal menstrual periods had been treated for four months by oral iron, without any effect (Hgb 10.2 g%, Fe 36.8%, ferritin < 10.8 mg%). On endoscopy of upper gastrointestinal tract there were macroscopic typical changes of H. pylori infection in antrum part of the stomach. On histological examination of biopsy segments inflammation of stomach mucosa in average intensification and H. pylori infection was confirmed. Recovery caused normalization of iron in the organism and of erythrocyte morphology. There was no recurrence of anaemia in long-term observation of the girl. A 14 years old boy treated without success for severe sideropenic anaemia (Hgb 7.1 g%), with positive family history (father has gastric ulcer). In spite of lack of gastrointestinal tract symptoms, on endoscopy there were features of chronic active hemorrhagic inflammation of stomach mucosa with H. pylori infection. Oral iron and effective eradication (proton pump inhibitor, amoxycillin, clarithromycin), achieved normalization of morphological changes. Recurrence of anaemia has not been observed.

Complications and antireflux medication use after antireflux surgery.

BACKGROUND & AIMS: Although antireflux surgery is increasingly common, few studies have assessed the associated complications and health care use after surgery. The aim of this study was to estimate postoperative complications and continued use of antireflux medications and to identify predictors of complications. METHODS: Through a review of the Department of Veterans Affairs administrative databases, all patients undergoing antireflux surgery from October 1, 1990, through January 29, 2001, were identified. Of 3367 patients identified, 222 were excluded as a result of a diagnosis of esophageal cancer, achalasia, or because there was no diagnosis related to gastroesophageal reflux disease. Medication use was determined for 2406 patients who had a minimum of 1 year of follow-up, including 1 or more outpatient visits at least 6 months after surgery and during the time when national pharmacy records were available. RESULTS: Dysphagia was recorded in 19.4%, dilation was performed in 6.4%, and a repeat antireflux surgery was performed in 2.3%. The surgical mortality rate was .8%. Prescriptions were dispensed repeatedly for H2 receptor antagonists in 23.8%, proton pump inhibitors in 34.3%, and promotility agents in 9.2% of patients. Overall, 49.8% of patients received at least 3 prescriptions for one of these medications. CONCLUSIONS: A moderate proportion of patients undergoing antireflux surgeries experienced complications and approximately 50% of patients received multiple prescriptions for antireflux medications at a median of 5 years of follow-up evaluation. Therefore, before surgery is performed, patients considering surgery should be counseled fully about the risk for complications and the likelihood of continued antireflux medication use.

A 9 year prospective cohort study of endoscoped patients with upper gastrointestinal symptoms.

Despite the high prevalence of upper gastrointestinal symptoms and associated costs of diagnosis and management, evidence regarding long-term outcomes is scant. We studied symptom outcomes 18 months (FU1) and 8/9 years (FU2) post-index endoscopy to identify demographic, diagnostic and treatment factors associated with outcomes. A retrospective review of medical records at two Australian teaching hospitals identified a cohort of 302 patients who had an index endoscopy (performed by 23 endoscopists) 18 months previously. Patients were interviewed at FU1 and FU2. In total 34% (95%CI: 29.0 39.8) of patients were asymptomatic at FUI and 41% (95%CI: 35.6-46.6) at FU2. For 63%, outcomes at FUI predicted long-term outcome, with 19% (95%CI: 14.6-23.4) asymptomatic and 44% (95%CI: 38.4-50.0) symptomatic at both times. Those whose symptom status changed were as likely to deteriorate as improve (p > 0.05). Number and severity of presenting symptoms (F = 3.3, df = 3,277, p < 0.05) and older age (F = 2.8, df = 2,301, p < 0.05) were associated with poorer outcomes. Long-term outcome was unrelated to endoscopic diagnosis. Those symptomatic were significantly more likely to be on proton pump inhibitors (PPIs) or Histamine2 Receptor Antagonists (H2RAs) than those who were asymptomatic. Use of PPIs at FU2 was associated with a significantly better outcome than use of H2RAs. However this impact was relatively small, with 69% of patients on PPIs and 84% on H2RAs symptomatic at FU2. Upper gastrointestinal symptoms prompting endoscopy are chronic for the majority of patients regardless of diagnosis. Endoscopic diagnosis is of limited value in predicting long-term outcomes. The association between poor outcome and use of H2RAs and PPIs challenges views about their long-term effectiveness in symptom control.

Gastroesophageal reflux disease poorly responsive to single-dose proton pump inhibitors in patients without Barrett's esophagus: acid reflux, bile reflux, or both?

OBJECTIVES: Studies using ambulatory pH and esophageal bile reflux monitoring (Bilitec) have shown that both acid reflux and duodeno-gastro-esophageal reflux (DGER) frequently occur in patients with gastroesophageal reflux disease (GERD). A subset of patients with GERD has persistent reflux symptoms in spite of standard doses of proton pump inhibitors (PPIs). The aim of the present study was to investigate the role of acid and DGER in patients with reflux disease poorly responsive to PPIs. METHODS: Sixty-five patients (32 men, 44 +/- 2 yr) without Barrett's esophagus and with persistent heartburn or regurgitation during standard PPI doses were studied. They underwent upper gastrointestinal endoscopy and simultaneous 24-h ambulatory pH and Bilitec monitoring while PPIs were continued. RESULTS: Thirty-three patients (51%) had persistent esophagitis. Seven patients (11%) had only pathological acid exposure, 25 (38%) had only pathological DGER exposure, and 17 (26%) had pathological exposure to both acid and DGER. Acid exposure under PPI was positive in only 37%, but adding Bilitec increased the diagnoses of persistent reflux to 75%. Patients with persistent esophagitis had similar acid exposure, but significantly higher DGER exposure than those without esophagitis. The highest prevalence of esophagitis was found in patients with pathological exposure to both acid and DGER; symptoms did not differ according to the type of reflux. CONCLUSIONS: Combined pH and Bilitec monitoring is superior to pH monitoring alone in demonstrating ongoing pathological reflux in patients with medically poorly responsive reflux disease.

High-dose intravenous proton pump inhibition following endoscopic therapy in the acute management of patients with bleeding peptic ulcers in the USA and Canada: a cost-effectiveness analysis.

BACKGROUND: The efficacy of high-dose intravenous proton pump inhibition has recently been shown, yet its cost-effectiveness remains poorly studied. AIM: To assess the cost-effectiveness of this approach separately for American and Canadian health care settings. METHODS: A validated decision model included patients with bleeding ulcers after successful endoscopic haemostasis. Probabilities were determined from the literature, and charges and lengths of stay from national databases. A third-party payer perspective was adopted over a 30-day time horizon. RESULTS: Re-bleeding rates were 5.9% for patients who received high-dose intravenous proton pump inhibition and 22.9% for those who did not. Hospitalization costs for patients with and without re-bleeding were 11,802 US dollars and 7993 US dollars, and 5220 Canadian dollars and 2696 Canadian dollars, respectively. High-dose intravenous proton pump inhibition was more effective and less costly than the alternative of not administering it. The cost-effectiveness ratios for high-dose and no high-dose intravenous proton pump inhibition were 9112 US dollars and 11,819 US dollars (3293 dollars and 4284 dollars for the Canadian case), respectively. Sensitivity and threshold analyses showed that the results were robust across a wide range of clinically relevant assumptions. CONCLUSION: In the USA and Canada, administering high-dose intravenous proton pump inhibition for 3 days is both more effective and less costly than not doing so for patients with bleeding ulcers after successful endoscopic haemostasis.

Benefits of different drug formulations in psychopharmacology.

Adequate dosage forms are essential for achieving successful pharmacotherapy. Innovative dosage forms or delivery systems may direct a drug to its specific site of action, optimize the timing of the drug release, or increase comfort or convenience for the patient. Thus, such innovations may improve efficacy and tolerability and lead to improvements in health-related quality of life. Specialized dosage forms (e.g., depot injections, extended-release formulations) of several psychiatric agents have been extensively used. The latest addition is an orally disintegrating formulation of the antidepressant mirtazapine. This dosage form dissolves rapidly in the mouth and is convenient for the large proportion of patients who have difficulty in swallowing tablets.

Overuse of acid suppressant drugs in patients with chronic renal failure.

BACKGROUND: Patients with chronic renal failure (CRF) have a high prevalence of gastrointestinal symptoms. The use of acid suppressive therapy (AST) in these patients is unexplored. We assessed the use of and indication for AST in CRF patients and compared them with hospitalized patients and patients with another chronic disease. METHODS: A total of 293 patients with CRF were compared with 261 hospitalized patients and 181 patients with another chronic disease. Information about AST, endoscopic investigations and indication for therapy were obtained by medical records and patient interviews. RESULTS: The use of AST was higher in CRF patients (41%, P<0.001) compared with hospitalized patients (13%) and patients with a chronic lung disease (18%), but similar in patients with a rheumatic disease (34%). Inadequate use of AST was high in CRF patients (63%) and hospitalized patients (81%), but lower in patients with another chronic disease (32%, P<0.01). Endoscopic investigations were performed in 41-46% of the patients. More than 90% of AST consisted of proton pump inhibitors (PPIs). CONCLUSION: The majority of CRF patients had an inadequate indication for AST. Endoscopy seemed to be underused in these patients. PPIs were the dominating acid suppressive drug.

Reasons for current practices in managing Barrett's esophagus.

We evaluated the reasons for current practices in managing Barrett's esophagus. Using a questionnaire, we assessed the practices and beliefs of 162 Californian gastroenterologists in managing Barrett's esophagus, using descriptive statistics as well as multivariate logistic regression. Out of the 103 respondents, 87% screened for Barrett's esophagus in patients with > 12 months of reflux symptoms, but only 72% believed that screening would improve survival, and 48% believed it to be cost-effective. In total, 98% surveyed patients with long-segment Barrett's esophagus at least biennially (76% thought this would improve survival and 49% believed it to be cost-effective) and 82% surveyed short-segment Barrett's esophagus at least biennially (57% thought this would improve survival and 30% believed it to be cost-effective). Finally, 44% surveyed microscopic intestinal metaplasia at least biennially (26% thought this would improve survival and 11% believed it to be cost-effective). In total, 18% performed endoscopic ablation, whereas 3% referred patients with low-grade dysplasia and 85% referred patients with high-grade dysplasia for esophagectomy. Finally, 81% treated asymptomatic Barrett's esophagus patients with proton pump inhibitors, but only 56% believed that this would reduce the risk of cancer. Logistic regression showed that the only independent factor predictive of surveillance practices was belief in efficacy. Practice patterns tend to be more aggressive than those recommended by recent guidelines and those reported by previous surveys. Medico-legal considerations affect practice substantially.

Pseudomembranous esophagitis.

BACKGROUND: Little is known of pseudomembranous esophagitis, a condition of striking endoscopic appearance. Presented here is a description of its nature and outcome. METHOD: Information on all patients with upper GI disease seen in our unit are held in a computerized database that includes presentation, diagnosis (including pseudomembranous esophagitis), treatment, and outcome. RESULTS: Forty-eight patients (mean age 70 years) with pseudomembranous esophagitis were seen over 15 years; 42 were in-patients with various illnesses. At endoscopy, a thin, concentric membrane and/or thick slough covered the distal half and occasionally the entire esophagus. This layer, yellow or blackened, could be peeled away to reveal underlying friable esophageal submucosa. The membrane was composed of fibrinous exudate and inflammatory cells; there was no basement membrane, hence the term pseudomembrane. Patients were treated with histamine H2 receptor antagonists or proton pump inhibitors for about 3 months and followed by endoscopy or clinical observation. All became asymptomatic; the pseudomembrane had disappeared in 32 who underwent follow-up endoscopy. It recurred in 3 of 38 being followed (mean 3.2 years), again associated with another illness requiring hospitalization. The long-term outcome was poor, determined by age and general condition and independent of pseudomembranous esophagitis. Seven patients died within 3 months and 17 during follow-up (mean 42 months, range 5-140 months). CONCLUSION: Pseudomembranous esophagitis is an unusual condition of unknown cause, probably under-reported and associated with systemic illness. It heals rapidly and recurrence is uncommon.

Tratamiento de la infección por helicobacter pylori en pacientes con úlcera duodenal: estudio de costo beneficio / Treatment of helicobacter pylori infection in patients with duodenal ulcer: a cost benefit study

Background: Epidemiological differences suggest that treatments for H. pylori eradication should be locally validated. Aim: To perform a cost benefit study of different treatment options for H. pylori infection. Patients and methods: One hundred and sixty-seven patients with active duodenal ulcer and H. pylori infection who completed a 2-week treatment with one of the following regimens were included: famotidine plus amoxycillin plus metronidazole (FAM), omeprazole plus amoxycillin plus tinidazole (OAT) or lansoprazole plus clarithromycin plus amoxycillin in 3 (LAC1) or 2 (LAC2) daily doses. We compared efficacy, adverse effects and cost. Results: Eradication rate was 74.6, 72.9, 96.4 y 91.7 percent for FAM, OAT, LAC1 and LAC2 respectively (p<0.05). Direct cost ranged from US$ 50 for FAM to US$ 220 for LAC1. A decision analysis was carried out in a model including direct and indirect costs and considering retreatment with antibiotics after the first treatment failure and one-year treatment with H2-blockers in case of a second failure. FAM was selected as the most cost-effective option, with an estimated cost of about US$ 300 ñ 148 per patient. However, cost associated to LAC2 was very similar (US$ 320 ñ 58) and the lower standard deviation suggests less variation. Sensitivity analyses, considering reasonable fluctuation in parameters such as eradication rate, cost and follow-up period suggest that a regimen containing a proton pump inhibitor, clarithromycin and amoxycillin may be the most cost-effective treatment. Conclusions: These results should be confirmed in other settings, specially in ordinary clinical practice, far from clinical research