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GOALS: Develop quality indicators for ineffective esophageal motility (IEM). BACKGROUND: IEM is identified in up to 20% of patients undergoing esophageal high-resolution manometry (HRM) based on the Chicago Classification. The clinical significance of this pattern is not established and management remains challenging. STUDY: Using RAND/University of California, Los Angeles Appropriateness Methods, we employed a modified-Delphi approach for quality indicator statement development. Quality indicators were proposed based on prior literature. Experts independently and blindly scored proposed quality statements on importance, scientific acceptability, usability, and feasibility in a 3-round iterative process. RESULTS: All 10 of the invited esophageal experts in the management of esophageal diseases invited to participate rated 12 proposed quality indicator statements. In round 1, 7 quality indicators were rated with mixed agreement, on the majority of categories. Statements were modified based on panel suggestion, modified further following round 2's virtual discussion, and in round 3 voting identified 2 quality indicators with comprehensive agreement, 4 with partial agreement, and 1 without any agreement. The panel agreed on the concept of determining if IEM is clinically relevant to the patient's presentation and managing gastroesophageal reflux disease rather than the IEM pattern; they disagreed in all 4 domains on the use of promotility agents in IEM; and had mixed agreement on the value of a finding of IEM during anti-reflux surgical planning. CONCLUSION: Using a robust methodology, 2 IEM quality indicators were identified. These quality indicators can track performance when physicians identify this manometric pattern on HRM. This study further highlights the challenges met with IEM and the need for additional research to better understand the clinical importance of this manometric pattern.
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INTRODUCTION: High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We aimed to assess the interrater agreement and accuracy of HRM and FLIP interpretations. METHODS: Esophageal motility specialists from multiple institutions completed the interpretation of 40 consecutive HRM and 40 FLIP studies. Interrater agreement was assessed using intraclass correlation coefficient (ICC) for continuous variables and Fleiss' κ statistics for nominal variables. Accuracies of rater interpretation were assessed using the consensus of 3 experienced raters as the reference standard. RESULTS: Fifteen raters completed the HRM and FLIP studies. An excellent interrater agreement was seen in supine median integral relaxation pressure (ICC 0.96, 95% confidence interval 0.95-0.98), and a good agreement was seen with the assessment of esophagogastric junction (EGJ) outflow, peristalsis, and assignment of a Chicago Classification version 4.0 diagnosis using HRM (κ = 0.71, 0.75, and 0.70, respectively). An excellent interrater agreement for EGJ distensibility index and maximum diameter (0.91 [0.90-0.94], 0.92 [0.89-0.95]) was seen, and a moderate-to-good agreement was seen in the assignment of EGJ opening classification, contractile response pattern, and motility classification (κ = 0.68, 0.56, and 0.59, respectively) on FLIP. Rater accuracy for Chicago Classification version 4.0 diagnosis on HRM was 82% (95% confidence interval 78%-84%) and for motility diagnosis on FLIP Panometry was 78% (95% confidence interval 72%-81%). DISCUSSION: Our study demonstrates high levels of interrater agreement and accuracy in the interpretation of HRM and FLIP metrics and moderate-to-high levels for motility classification in FLIP, supporting the use of these approaches for primary or complementary evaluation of esophageal motility disorders.
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Acalasia Esofágica , Transtornos da Motilidade Esofágica , Humanos , Reprodutibilidade dos Testes , Transtornos da Motilidade Esofágica/diagnóstico , Junção Esofagogástrica/diagnóstico por imagem , Manometria/métodos , Peristaltismo , Acalasia Esofágica/diagnósticoRESUMO
BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) therapy has been shown to be a safe and effective treatment for advanced Parkinson's disease (PD). Limited data are available regarding long-term benefits and complications in Canada. Objective of the study was to review long-term experience and clinical outcomes in PD patients with LCIG therapy over 11 years in a multidisciplinary University clinic setting. METHODS: Chart review was done on PD patients with LCIG from 2011 to 2022. Data collected: dosing, UPDRS-III motor scores, OFF times, hours with dyskinesias, MoCA, complications, discontinuation reasons, and nursing time requirements. RESULTS: Thirty-three patients received LCIG therapy with a mean follow-up of 3.25±2.09 years. UPDRS-III scores showed reduction of 15% from baseline (mean 35.9) up to 4 years (mean 30.4). Daily OFF time improved from baseline (mean 7.1 ± 3.13 hours) up to 5 years (mean 3.3 ± 2.31 hours; -53.5%; p < 0.048), and dyskinesias remained stable. Nursing time averaged 22 hours per patient per year after PEG-J insertion and titration. Most common complications were PEG-J tube dislodgement and stoma site infection (0-3zero to three events/patient/year). Serious side effects were seen in four (12%) patients resulting in hospitalization and/or death. Nine patients (27.2%) discontinued the treatment due to lack of improved efficacy over oral therapy or development of dementia and 10 (30%) died of causes unrelated to LCIG infusion. CONCLUSION: Patients on LCIG showed improved motor function over 5-year follow-up. Serious complications were uncommon. Dedicated nursing time is required by LCIG-trained nurses in a multidisciplinary setting for optimum management.
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UNLABELLED: Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality. OBJECTIVES: To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults. METHODS: A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria. CONCLUSIONS: Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.
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Analgésicos Opioides/efeitos adversos , Constipação Intestinal/tratamento farmacológico , Laxantes/uso terapêutico , Adulto , Catárticos/efeitos adversos , Catárticos/farmacologia , Catárticos/uso terapêutico , Constipação Intestinal/induzido quimicamente , Ácido Dioctil Sulfossuccínico/efeitos adversos , Ácido Dioctil Sulfossuccínico/farmacologia , Ácido Dioctil Sulfossuccínico/uso terapêutico , Humanos , Lactulose/efeitos adversos , Lactulose/farmacologia , Lactulose/uso terapêutico , Laxantes/efeitos adversos , Laxantes/farmacologia , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Extrato de Senna/efeitos adversos , Extrato de Senna/farmacologia , Extrato de Senna/uso terapêutico , Tensoativos/efeitos adversos , Tensoativos/farmacologia , Tensoativos/uso terapêuticoRESUMO
Objectives: To identify irritable bowel syndrome (IBS) patients' attitudes, subjective norms, perceived control and intention to practice yoga and gastroenterologists' attitudes and current yoga recommendations for their patients with IBS. Methods: Gastroenterologists and IBS patients completed online surveys including Theory of Planned Behaviour (TPB) constructs. Among IBS patients, multiple linear regression determined the multivariate associations between TPB variables and intention to practice yoga while controlling for significant socio-demographic variables. Gastroenterologists were asked about their attitudes and current yoga recommendations for patients with IBS. Chi-square analyses examined associations between gastroenterologists' demographics and recommending yoga. Binomial logistic regression described associations between attitude variables and current yoga recommendations. Results: For patients (n = 109), controllability (ß = 0.5, P < 0.001), affective attitude (ß = 0.4, P < 0.05) and self-efficacy (ß = 0.3, P < 0.05) were significantly associated with intention to do yoga in the regression model. TPB variables explained 34% of the variance in patients' intentions to practice yoga. The binomial regression analysis revealed that gastroenterologists (n = 79) who have confidence in recommending yoga (39%) were seven times more likely to recommend it (odds ratio = 7.3, P = 0.002) and those who agreed yoga improves IBS symptom severity (54%) were 10 times more likely to recommend yoga (odds ratio = 10.1, P < 0.001). Most (86%) wanted more evidence to support efficacy of yoga for IBS and 44% asked for more knowledge on how to refer a patient. Conclusion: Controllability, affective attitude and self-efficacy predicted IBS patients' intentions to practice yoga. Although gastroenterologists believed yoga is safe and beneficial for IBS patients, most do not recommend yoga due to lack of confidence and scientific evidence.
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BACKGROUND: Wireless capsule pH-metry (WC) is better tolerated than standard nasal pH catheter (SC), but endoscopic placement is expensive. AIMS: to confirm that non-endoscopic peroral manometric placement of WC is as effective and better tolerated than SC and to perform a cost analysis of the available esophageal pH-metry methods. METHODS: Randomized trial at 2 centers. Patients referred for esophageal pH testing were randomly assigned to WC with unsedated peroral placement or SC after esophageal manometry (ESM). Primary outcome was overall discomfort with pH-metry. Costs of 3 different pH-metry strategies were analyzed: 1) ESM + SC, 2) ESM + WC and 3) endoscopically placed WC (EGD + WC) using publicly funded health care system perspective. RESULTS: 86 patients (mean age 51 ± 2 years, 71% female) were enrolled. Overall discomfort score was less in WC than in SC patients (26 ± 4 mm vs 39 ± 4 mm VAS, respectively, p = 0.012) but there were no significant group differences in throat, chest, or overall discomfort during placement. Overall failure rate was 7% in the SC group vs 12% in the WC group (p = 0.71). Per patient costs ($Canadian) were $1475 for EGD + WC, $1014 for ESM + WC, and $906 for ESM + SC. Decreasing the failure rate of ESM + WC from 12% to 5% decreased the cost of ESM + WC to $991. The ESM + SC and ESM + WC strategies became equivalent when the cost of the WC device was dropped from $292 to $193. CONCLUSIONS: Unsedated peroral WC insertion is better tolerated than SC pH-metry both overall and during placement. Although WC is more costly, the extra expense is partially offset when the higher patient and caregiver time costs of SC are considered. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT01364610.
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Cápsulas/economia , Catéteres/economia , Monitoramento do pH Esofágico/economia , Monitoramento do pH Esofágico/instrumentação , Refluxo Gastroesofágico/diagnóstico , Custos e Análise de Custo , Feminino , Humanos , Incidência , Masculino , Manometria/instrumentação , Pessoa de Meia-Idade , Dor/epidemiologia , Medição da Dor , Estudos RetrospectivosRESUMO
Esophageal hypomotility disorders manifest with abnormal esophageal body contraction vigor, breaks in peristaltic integrity, or failure of peristalsis in the context of normal lower esophageal sphincter relaxation on esophageal high-resolution manometry (HRM). The Chicago Classification version 4.0 recognizes two hypomotility disorders, ineffective esophageal motility (IEM) and absent contractility, while fragmented peristalsis has been incorporated into the IEM definition. Updated criteria for ineffective swallows consist of weak esophageal body contraction vigor measured using distal contractile integral (DCI, 100-450 mmHg·cm·s), transition zone defects >5 cm measured using a 20 mmHg isobaric contour, or failure of peristalsis (DCI < 100 mmHg·cm·s). More than 70% ineffective swallows and/or ≥50% failed swallows are required for a conclusive diagnosis of IEM. When the diagnosis is inconclusive (50%-70% ineffective swallows), supplementary evidence from multiple rapid swallows (absence of contraction reserve), barium radiography (abnormal bolus clearance), or HRM with impedance (abnormal bolus clearance) could support a diagnosis of IEM. Absent contractility requires 100% failed peristalsis, consistent with previous versions of the classification. Consideration needs to be given for the possibility of achalasia in absent contractility with dysphagia despite normal IRP, and alternate complementary tests (including timed upright barium esophagram and functional lumen imaging probe) are recommended to confirm or refute the presence of achalasia. Future research to quantify esophageal bolus retention on stationary HRM with impedance and to understand contraction vigor thresholds that predict bolus clearance will provide further refinement to diagnostic criteria for esophageal hypomotility disorders in future iterations of the Chicago Classification.
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Transtornos da Motilidade Esofágica/diagnóstico , Esôfago/fisiopatologia , Trânsito Gastrointestinal/fisiologia , Transtornos da Motilidade Esofágica/fisiopatologia , Humanos , ManometriaRESUMO
Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.
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Transtornos da Motilidade Esofágica/fisiopatologia , Manometria/métodos , Acalasia Esofágica/classificação , Acalasia Esofágica/diagnóstico , Acalasia Esofágica/fisiopatologia , Acalasia Esofágica/terapia , Transtornos da Motilidade Esofágica/classificação , Transtornos da Motilidade Esofágica/diagnóstico , Transtornos da Motilidade Esofágica/terapia , Espasmo Esofágico Difuso/classificação , Espasmo Esofágico Difuso/diagnóstico , Espasmo Esofágico Difuso/fisiopatologia , Espasmo Esofágico Difuso/terapia , Junção Esofagogástrica/fisiopatologia , HumanosRESUMO
The introduction of acid inhibition in clinical practice has revolutionized the management of acid-related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating antireflux surgery to patients with gastroesophageal reflux disease (GERD) not adequately managed by medical therapy. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for the treatment of reflux disease. However, these drugs still leave some unmet clinical needs in GERD. PPI-refractoriness is common, and persistent symptoms are observed in up to 40-55% of daily PPI users. Potassium-competitive acid blockers (P-CABs) clearly overcome many of the drawbacks and limitations of PPIs, achieving rapid, potent, and prolonged acid suppression, offering the opportunity to address many of the unmet needs. In recent years, it has been increasingly recognized that impaired mucosal integrity is involved in the pathogenesis of GERD. As a consequence, esophageal mucosal protection has emerged as a new, promising therapeutic avenue. When P-CABS are used as add-on medications to standard treatment, a growing body of evidence suggests a significant additional benefit, especially in the relief of symptoms not responding to PPI therapy. On the contrary, reflux inhibitors are considered a promise unfulfilled, and prokinetic agents should only be used on a case-by-case basis.
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Mucosa Esofágica/patologia , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Cimetidina/uso terapêutico , Esomeprazol/uso terapêutico , Refluxo Gastroesofágico/diagnóstico , Humanos , Lansoprazol/uso terapêutico , Omeprazol/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêuticoRESUMO
BACKGROUND: Gastrointestinal (GI) motility and functional disorders comprise over two-third of referrals to GI specialists yet training programs are disproportionately focused on endoscopy, inflammatory bowel disease and liver disease. Trainees at many centres receive minimal or no formal training in motility disorders and have little or no exposure to motility testing. Our purpose was to develop an educational intervention to address this learning need. METHODS: We designed a formal training program comprised of didactic sessions, workshops and hands-on motility sessions with live demonstrations designed to be held over the course of a weekend. Faculty for the course were experienced GI motility experts from across Canada. Resident trainees from all Canadian GI fellowship programs were invited to attend. Pre- and post-tests were administered to measure the baseline learning needs and the impact of the program. Course evaluations were completed by attendees. RESULTS: Three annual courses were offered over the past 3 years. Both adult and paediatric gastroenterology trainees attended the programs. The majority of training programs from Canada were represented. Baseline testing of attendees revealed a fundamental lack of understanding of GI motility concepts and their clinical implications. Postcourse test scores demonstrated a significant improvement in motility knowledge. Course evaluations of the content and faculty presentations received uniformly positive reviews. CONCLUSIONS: There is a pervasive lack of clinical knowledge of GI motility among Canadian GI subspecialty trainees. A focused weekend intensive course is one step in addressing this learning need.
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Esophageal dysphagia is a common symptom in adults. Fluoroscopic contrast studies, endoscopy, and esophageal manometry have been used in the diagnosis of esophageal dysphagia for many years. The diagnostic yield has been improved with new test protocols that highlight abnormal bolus transit in the esophagus and outflow obstruction, as well as new high-definition and high-resolution technical advances in equipment. Functional luminal impedance planimetry and the addition of impedance to high-resolution esophageal manometry have also allowed the assessment of new parameters to better understand esophageal structure and function. In this concise review, we describe the role and utility of various diagnostic modalities in the assessment of patients with esophageal dysphagia.
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Transtornos da Motilidade Esofágica , Esôfago/fisiopatologia , Adulto , Impedância Elétrica , Transtornos da Motilidade Esofágica/diagnóstico , Transtornos da Motilidade Esofágica/diagnóstico por imagem , Transtornos da Motilidade Esofágica/fisiopatologia , Feminino , Fluoroscopia , Humanos , Masculino , ManometriaRESUMO
Fecal incontinence is a common disorder in our aging population and can have profound effects on patient's well-being. The present review examines the current understanding of fecal incontinence and provides a practical approach to the investigation and management of this condition. A special emphasis is placed on specialized testing, focusing on indications and impact on guiding management.
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Incontinência Fecal/diagnóstico , Incontinência Fecal/terapia , Idoso , Idoso de 80 Anos ou mais , Canal Anal/diagnóstico por imagem , Canal Anal/fisiopatologia , Incontinência Fecal/etiologia , Incontinência Fecal/fisiopatologia , Feminino , Humanos , Manometria/métodos , UltrassonografiaRESUMO
BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders, affecting about 10% of the general population globally. The aim of this consensus was to develop guidelines for the management of IBS. METHODS: A systematic literature search identified studies on the management of IBS. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a multidisciplinary group of clinicians and a patient. RESULTS: Consensus was reached on 28 of 31 statements. Irritable bowel syndrome is diagnosed based on symptoms; serological testing is suggested to exclude celiac disease, but routine testing for C-reactive protein (CRP), fecal calprotectin or food allergies is not recommended. A trial of a low fermentable oligosaccharides, disaccharides, monosaccharides, polyols (FODMAP) diet is suggested, while a gluten-free diet is not. Psyllium, but not wheat bran, supplementation may help reduce symptoms. Alternative therapies such as peppermint oil and probiotics are suggested, while herbal therapies and acupuncture are not. Cognitive behavioural therapy and hypnotherapy are suggested psychological therapies. Among the suggested or recommended pharmacological therapies are antispasmodics, certain antidepressants, eluxadoline, lubiprostone, and linaclotide. Loperamide, cholestyramine and osmotic laxatives are not recommended for overall IBS symptoms. The nature of the IBS symptoms (diarrhea-predominant or constipation-predominant) should be considered in the choice of pharmacological treatments. CONCLUSIONS: Patients with IBS may benefit from a multipronged, individualized approach to treatment, including dietary modifications, psychological and pharmacological therapies.
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BACKGROUND AND AIM: The value of a multidisciplinary group and patient engagement in guideline groups is uncertain. We compared the recommendations of two guidelines that used the same data during the same time frame but with different participants to obtain a "real world" perspective on influence of the composition of guideline groups. METHODS: The Canadian Association of Gastroenterology (CAG) and the American College of Gastroenterology (ACG) recently updated their clinical practice guidelines for the management of Irritable Bowel Syndrome (IBS). Both the CAG and ACG used the same methodology and methodologist and were presented with the same data for interpretation. The ACG group consisted of predominantly academic gastroenterologists, while the CAG group also included general practitioners, a psychiatrist, a psychologist and a patient representative. The CAG group were also asked what components of the group were valuable. RESULTS: There were 14 statements with the same or similar recommendations. There were 10 statements in the CAG guideline not addressed by the ACG guideline and five recommendations where the opposite was the case. There was one statement that the two groups both addressed, but each group came to different conclusions. CAG members were in 100% agreement that involving a patient and having a multidisciplinary team was valuable and may have played a role in these differing interpretations of the same data in an IBS guideline. CONCLUSIONS: There has been little uptake of patient involvement and multidisciplinary teams in guideline groups. However, this study provides a unique example of added benefit through broader group representation.
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BACKGROUND AND AIMS: Our aim is to review the literature and provide guidelines for the assessment of uninvestigated dysphagia. METHODS: A systematic literature search identified studies on dysphagia. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Statements were discussed and revised via small group meetings, teleconferences, and a web-based platform until consensus was reached by the full group. RESULTS: The consensus includes 13 statements focused on the role of strategies for the assessment of esophageal dysphagia. In patients presenting with dysphagia, oropharyngeal dysphagia should be identified promptly because of the risk of aspiration. For patients with esophageal dysphagia, history can be used to help differentiate structural from motility disorders and to elicit alarm features. An empiric trial of proton pump inhibitor therapy should be limited to four weeks in patients with esophageal dysphagia who have reflux symptoms and no additional alarm features. For patients with persistent dysphagia, endoscopy, including esophageal biopsy, was recommended over barium esophagram for the assessment of structural and mucosal esophageal disease. Barium esophagram may be useful when the availability of endoscopy is limited. Esophageal manometry was recommended for diagnosis of esophageal motility disorders, and high-resolution was recommended over conventional manometry. CONCLUSIONS: Once oropharyngeal dysphagia is ruled out, patients with symptoms of esophageal dysphagia should be assessed by history and physical examination, followed by endoscopy to identify structural and inflammatory lesions. If these are ruled out, then manometry is recommended for the diagnosis of esophageal dysmotility.
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Esophageal symptoms can arise from gastroesophageal reflux disease (GERD) as well as other mucosal and motor processes, structural disease, and functional esophageal syndromes. GERD is the most common esophageal disorder, but diagnosis may not be straightforward when symptoms persist despite empiric acid suppressive therapy and when mucosal erosions are not seen on endoscopy (as for nonerosive reflux disease, NERD). Esophageal physiological tests (ambulatory pH or pH-impedance monitoring and manometry) can be of value in defining abnormal reflux burden and reflux-symptom association. NERD diagnosed on the basis of abnormal reflux burden on ambulatory reflux monitoring is associated with similar symptom response from antireflux therapy for erosive esophagitis. Acid suppression is the mainstay of therapy, and antireflux surgery has a definitive role in the management of persisting symptoms attributed to NERD, especially when the esophagogastric junction is compromised. Adjunctive approaches and complementary therapy may be of additional value in management. In this review, we describe the evaluation, diagnosis, differential diagnosis, and management of NERD.
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Monitoramento do pH Esofágico/métodos , Junção Esofagogástrica , Esofagoscopia/métodos , Refluxo Gastroesofágico , Junção Esofagogástrica/metabolismo , Junção Esofagogástrica/fisiopatologia , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/metabolismo , Refluxo Gastroesofágico/fisiopatologia , Humanos , Manometria/métodosAssuntos
Antiparkinsonianos/farmacologia , Carbidopa/farmacologia , Hipoventilação/tratamento farmacológico , Levodopa/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Antiparkinsonianos/administração & dosagem , Carbidopa/administração & dosagem , Depressão/tratamento farmacológico , Combinação de Medicamentos , Feminino , Géis , Humanos , Infusões Parenterais , Jejunostomia , Levodopa/administração & dosagem , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Obstructive sleep apnea (OSA) increases the risk for mild hypertension, but its relationship to refractory hypertension (RHT) has not been systematically examined. We previously reported a high prevalence of OSA in patients with RHT, but did not have a control group with which to compare. Rapid eye movement (REM) sleep deprivation can raise blood pressure in animals. However, a potential relationship of OSA and REM sleep time with RHT has not been examined. OBJECTIVE: To determine whether, compared with patients with well controlled hypertension, those with RHT have a higher prevalence of OSA (apnea-hypopnea index > or = 10 per hour of sleep) and shorter REM sleep time. METHODS: We compared the prevalence of OSA and sleep structure in 42 patients with RHT with 22 patients with controlled hypertension, matched for age, sex and BMI. RESULTS: Compared with the controlled hypertension group, the RHT group had a significantly higher prevalence of OSA (81 versus 55%, P = 0.03) and less REM sleep time (47.0 +/- 4.5 versus 63.2 +/- 4.9 min, P = 0.02). Multivariate analysis revealed significantly increased odds of having RHT associated with OSA independent of other risk factors (adjusted odds ratio, 3.994; 95% confidence interval, 1.191-13.388). Reduced REM sleep time was also independently associated with the presence of RHT (adjusted odds ratio, 1.025; 95% confidence interval, 1.002-1.049). CONCLUSION: OSA and reduced REM sleep time are associated with increased odds of having RHT and, therefore, may play roles in its pathogenesis.
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Hipertensão/complicações , Apneia Obstrutiva do Sono/complicações , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sono REMRESUMO
BACKGROUND & AIMS: Typical hemochromatosis patients are homozygous for the C282Y mutation of the HFE gene. However, approximately 50% of women and 20% of men do not have an increase in serum ferritin level. This study assessed factors, genetic and otherwise, that may modify biochemical expression in C282Y homozygotes. METHODS: Hemochromatosis families that each had at least 2 untreated C282Y homozygotes were included. Nonexpressors were defined as having a ferritin level less than 300 microg/L for a male and a ferritin level less than 200 microg/L for a female. A multivariate linear stepwise regression analysis was performed to assess the contribution of sex, age, and the presence of a nonexpressor in the family on serum ferritin level. Heritability calculations were performed using variance component analysis. RESULTS: Fifty-three pedigrees consisting of 148 C282Y homozygotes (92 males, 56 females) were identified. Twenty-nine homozygotes were nonexpressors (19.6%), of which 11 of 29 were male (37.9%) (P=.0054). Based on multivariate analysis, highly significant associations with increased ferritin levels in C282Y homozygotes were male sex (P=.00005), increasing age (P=.009), and absence of a nonexpressor in the family (P=.01). Variance component modeling using age, sex, and C282Y genotype as covariates in 39 pedigrees (n=296) showed a residual heritability for serum ferritin of .35+/-.10 (P<.001). CONCLUSIONS: These findings suggest that male sex is the major clinical factor associated with an increased serum ferritin level in hemochromatosis. In addition, these results support the hypothesis that other genes contribute to the variance in serum ferritin concentration among C282Y homozygotes.