The impact of gastroesophageal reflux disease symptoms in scleroderma: effects on sleep quality.

Systemic scleroderma/sclerosis (SSc) is an autoimmune connective tissue disease, which can lead to esophageal motor dysfunction and gastroesophageal reflux disease (GERD). Nocturnal GERD symptoms may be associated with sleep disturbances, which in turn can drastically affect well-being and fatigue levels. We hypothesized that GERD symptoms would be associated with poorer sleep in patients with SSc. Rheumatologist established SSc patients completed the following questionnaires: the UCLA scleroderma clinical trial consortium gastrointestinal tract instrument (GIT) 2.0 questionnaire; the Pittsburgh sleep quality index (PSQI); the fatigue severity scale (FSS); the multidimensional gastrointestinal symptom severity index (GSSI). Poor sleep quality was defined by a PSQI total score >5. Questionnaires were completed by 287 patients [mean (SD) age = 59 (14) years; female = 243]. Poor sleep quality was identified in 194 (68%) patients. Patients with poor sleep quality reported less sleep time and increased fatigue compared to those with normal sleep scores. SSc patients with poor sleep had significantly higher GIT Reflux scores (P < .001), and poor sleep was more frequent in those with moderate/severe versus mild/no heartburn on GISSI (P < .001). Narcotic and antidepressant use was significantly more frequent in SSc patients with poor sleep quality. Multivariable logistic regression supported the association between GERD symptoms and poor sleep after controlling for age, sex, and body mass index (BMI) (2.53, 95% confidence interval (CI) 1.52-4.25; P < .001). The association remained after controlling for narcotic and antidepressant use (2.20, 95% CI 1.29-3.73; P < .001). SSc patients who reported GERD symptoms were also more likely to report poor sleep quality. Future studies should examine mechanisms underlying nocturnal GERD symptoms in SSc patients, and the impact of improved GERD symptom control on sleep quality.

Do recent reports about the adverse effects of proton pump inhibitors change providers' prescription practice?

Proton pump inhibitors (PPI) are utilized for a variety of indications, including treatment of gastroesophageal reflux disease, peptic ulcer disease, and prevention of gastrointestinal (GI) bleeding. Several studies have documented an increasing prevalence of inappropriate PPI use. Furthermore, recent media reports have highlighted new research data suggesting a possible association between chronic PPI use and several adverse medical outcomes, leading to frequent patient inquiries about these associations. Thus, providers face the challenge of counseling patients about the balance of risks and benefits related to PPI use. We aimed to explore providers' knowledge and attitudes toward reported adverse effects of PPI use and compare providers' prescription practices. A comprehensive, non-incentivized electronic survey was sent to all providers (residents, fellows, advanced practice providers, and consultants across 8 internal medicine specialties) at our tertiary academic medical center. The survey contained 21 questions covering provider demographics and responses to challenging clinical scenarios dealing with PPI use. Chi-square was used to compare responses from providers. The survey was distributed to 254 providers, of which 94 (24 GI and 70 non-GI) completed the survey (37% response rate). Among those 94 providers, 48 were consultants, 17 were advanced practice providers, and 29 were trainees. Non-GI providers included cardiology, pulmonary, endocrinology, family medicine, general internal medicine, hematology/oncology, and nephrology. Over half of the providers (51 [54%]) described their practice as outpatient setting, 29 (31%) providers defined their practice as a mixed setting (inpatient and outpatient), while 14 (15%) designated it as inpatient only. Nineteen (80%) GI providers and 48 (69%) non-GI providers discussed the risks and benefits with patients (P = 0.64). Fifteen (63%) GI providers and 33 (47%) non-GI providers indicated that recent reports changed their practice (P = 0.49). More GI providers (5 [21%]) lowered the dose of PPI compared with non-GI (1[1%]) (P = 0.004); 18 (26%) of non-GI and 3 (13%) of GI providers discontinued PPI and substituted it with a histamine 2 (H2) blocker (P = 0.29). A larger but nonsignificant percentage of trainees (8 [28%]) switched PPI to H2 blockers compared with consultants (8 [17%]; P = 0.39). Six (25%) of GI providers and 14 (20%) of non-GI providers were concerned about Clostridium difficile infection (P = 0.58). Twenty-four (34%) of the non-GI were worried about kidney diseases compared with 3 (13%) of the GI providers (P = 0.1). Ten (21%) consultants were concerned about risk of osteoporosis compared with 3 (10%) trainees (P = 0.38), while 8 (28%) trainees were worried about the risk of C. difficile infection compared with 10 (21%) consultants (P = 0.69). Most providers (85 [90%]) agreed that educational activities would be helpful to address these challenges. More GI providers lowered the dose of PPI compared with non-GI; non-GI providers were more likely to discontinue PPI and substitute it with an H2 blocker. Educating patients and providers about potential adverse effects of PPI is imperative.

Esophageal dysmotility according to Chicago classification v3.0 vs v2.0: Implications for association with reflux, bolus clearance, and allograft failure post-lung transplantation.

BACKGROUND: Proximal reflux and incomplete transit of boluses swallowed are risk factors for obstructive chronic lung allograft dysfunction (o-CLAD) post-lung transplantation (LTx). Likewise, so is esophagogastric junction outflow obstruction (EGJOO), but not hypo-contractility, when diagnosed using Chicago Classification (CC) v3.0. Given, peristaltic breaks as defined using CCv2.0 can prolong esophageal clearance, both swallowed and refluxed, but which are deemed within normality using CCv3.0, our aim was to determine whether hypo-contractility as diagnosed using CCv2.0, influences the association with reflux, along with its clearance, and that of boluses swallowed, and thus its association to allograft failure. METHODS: Esophageal motility abnormalities were classified using CC v3.0 and v2.0 in 50 patients post-LTx (26 female, 55 years (20-73 years)). RESULTS: Reclassification from CCv3.0 to v2.0 resulted in 7 patients with normal motility being reclassified to hypo-contractility (n = 6) or hyper-contractility (n = 1); 2 patients with hypo-contractility to normal motility; and 3 patients with EGJOO without hyper-contractility to EGJOO with hyper-contractility. The main consequence of reclassification was that the sub-group exhibiting hypo-contractility became more likely to have abnormal numbers of reflux events (P = .025) and incomplete bolus transit (P = .002) than those with normal motility using CCv2.0; associations not seen using CCv3.0. Irrespective of CC used only patients with EGJOO appeared more likely to develop o-CLAD than those with normal motility (P < .05). CONCLUSIONS: Irrespective of CC used, o-CLAD appears linked to EGJOO. CCv2.0 however, accentuates the increased reflux and incomplete bolus transit associated with hypo-contractility post-LTx, suggesting that these motor abnormalities, though considered minor, may be of importance after lung transplant.

Clinical utility of gastric emptying scintigraphy: Patient and physician perspectives.

BACKGROUND: The use of gastric emptying scintigraphy (GES) in the evaluation of patients with dyspeptic symptoms is controversial. Our aim was to investigate objective and subjective parameters of clinical utility of GES from the perspectives of both the patient and the ordering physician. METHODS: Socio-demographic features, healthcare resource utilization, gastroparetic symptoms and quality of life (QoL) were obtained from consecutive patients referred for GES immediately prior to GES and again 4 months later. The ordering physician received a brief survey 2 weeks after the GES regarding their perceptions on whether the test provided them with clinically useful information. KEY RESULTS: One hundred and seventy-two (mean age ± SD 52.0 ± 17.9; 78% female) of 266 patients enrolled completed both the baseline and follow-up questionnaires and comprised our study population. At baseline, patients with abnormal GES had significantly higher gastroparesis symptom scores and reduced QoL. At the 4-month follow-up, an improvement in symptoms and QoL was seen, but the degree of improvement was not significantly different between those with a normal or abnormal GES. One hundred and ninety-seven ordering physicians completed the survey and perceived that GES, particularly when abnormal, provided new information (91%) and resulted in a change in diagnosis (58%) and management (60%). CONCLUSIONS & INFERENCES: Although patients with an abnormal GES generally had worse symptoms and lower QoL, the results of GES did not help to identify those with improved or worsened symptoms or QoL at follow-up. Nevertheless, the ordering physicians generally felt that the results of GES were helpful in managing these patients.

The clinical significance of hypercontractile peristalsis: comparison of high-resolution manometric features, demographics, symptom presentation, and response to therapy in patients with Jackhammer esophagus versus Nutcracker esophagus.

The Chicago Classification version 3.0 (CC v 3.0) defines hypercontractile peristalsis as Jackhammer esophagus (JE); Nutcracker esophagus (NE) is no longer recognized. Data regarding patient characteristics and treatment response for JE versus NE are limited. We aimed to compare demographic characteristics, high resolution manometry (HRM) features, clinical presentation, management strategies, and treatment outcomes in patients with JE versus NE. We performed a retrospective analysis of adult patients diagnosed with NE (CC v 2.0) or JE (CC v 3.0) by HRM from January 2012 to August 2015. Demographics, symptoms, treatments, and response to therapy (none or partial/complete) were ascertained by chart review, for statistical comparisons. In 45 patients with JE and 29 with NE, there was no significant difference in rate of dysphagia (73% and 59%) or chest pain (44% and 59%). Treatment data were available in 29 JE (smooth muscle relaxants in 4, pain modulators in 3, botulinum toxin injection (BTX) in 10, endoscopic dilation in 5, multimodal treatment in 7), and 20 NE patients (smooth muscle relaxants in 2, pain modulators in 2, (BTX) in 6, endoscopic dilation in 3, multimodal treatment in 7). Follow-up data on 26/29 JE and 20/20 NE patients showed similar treatment response (96.4% vs. 82.1%, p= 0.08) after mean follow-up of 11.2 and 11 months, respectively. There were no major differences for JE versus NE in demographics, symptoms, or type of and response to therapy. Larger prospective, controlled trials are needed to clarify the clinical significance and response to treatment in JE and NE.

Baseline impedance measured during high-resolution esophageal impedance manometry reliably discriminates GERD patients.

BACKGROUND: Baseline impedance measured with ambulatory impedance pH monitoring (MII-pH) and a mucosal impedance catheter detects gastroesophageal reflux disease (GERD). However, these tools are limited by cost or patient tolerance. We investigated whether baseline impedance measured during high-resolution impedance manometry (HRIM) distinguishes GERD patients from controls. METHODS: Consecutive patients with clinical HRIM and MII-pH testing were identified. Gastroesophageal reflux disease was defined by esophageal pH <4 for ≥5% of both the supine and total study time, whereas controls had an esophageal pH <4 for ≤3% of the study performed off PPI. Baseline impedance was measured over 15 seconds during the landmark period of HRIM and over three 10 minute intervals during the overnight period of MII-pH. KEY RESULTS: Among 29 GERD patients and 26 controls, GERD patients had a mean esophageal acid exposure time of 22.7% compared to 1.2% in controls (P<.0001). Mean baseline impedance during HRIM was lower in GERD (1061 Ω) than controls (2814 Ω) (P<.0001). Baseline mucosal impedance measured during HRIM and MII-pH correlated (r=0.59, P<.0001). High-resolution esophageal manometry baseline impedance had high diagnostic accuracy for GERD, with an area under the curve (AUC) of 0.931 on receiver operating characteristics (ROC) analysis. A HRIM baseline impedance threshold of 1582 Ω had a sensitivity of 86.2% and specificity of 88.5% for GERD, with a positive predictive value of 89.3% and negative predictive value of 85.2%. CONCLUSIONS & INFERENCES: Baseline impedance measured during HRIM can reliably discriminate GERD patients with at least moderate esophageal acid exposure from controls. This diagnostic tool may represent an accurate, cost-effective, and less invasive test for GERD.

The relationship among gastroparetic symptoms, quality of life, and gastric emptying in patients referred for gastric emptying testing.

BACKGROUND: Symptoms suggestive of gastroparesis are non-specific and conflicting reports exist regarding the ability of symptoms to predict the presence of gastroparesis. Our aim, therefore, was to evaluate the relationships between gastroparetic symptoms and their impact on quality of life and determine their relationship with clinical factors and gastric emptying. METHODS: Gastric emptying scintigraphy, sociodemographic features, health care resource utilization, gastroparetic symptoms, and quality of life using validated questionnaires were obtained from consecutive patients referred for gastric emptying testing (GET). Descriptive analyses were conducted and logistic regression was performed to evaluate associations with abnormal gastric emptying after controlling for other covariates. KEY RESULTS: Two hundred and sixty-six patients participated (195 females; mean age, 49.1 ± 17.6 years); 75% met Rome III criteria for functional dyspepsia. Gastric emptying was delayed in 28.2% at 4 h; the delay was mild in 48%, moderate in 20% and severe in 32%. Nausea/emesis and postprandial fullness, but not bloating, were significantly greater in those with delayed emptying. Postprandial fullness was most severe. Weak correlations were identified between symptom severity and the severity of gastric emptying delay. Quality of life was also lower in the delayed emptying group. Logistic regression analysis demonstrated associations between delayed gastric emptying and lower quality of life and increased symptom severity. CONCLUSIONS & INFERENCES: In patients referred for GET, gastroparetic symptoms were more severe in those with delayed emptying. A decrease in quality of life in those with delayed gastric emptying was also present; this was not related to the severity of the delay in gastric emptying.

Psychological distress in Rome III functional dyspepsia patients presenting for testing of gastric emptying.

BACKGROUND: There have been conflicting results from studies that have evaluated psychological disturbances in functional dyspepsia (FD). We conducted a comprehensive survey of psychological measures in patients undergoing gastric emptying testing (GET) in order to determine the relationship among psychological distress, gastric emptying, and dyspeptic symptoms. METHODS: Consecutive patients referred for GET were prospectively enrolled. Details regarding patient characteristics, health care utilization, dyspeptic symptoms, quality of life, and psychological dysfunction were obtained. Depression, anxiety, somatization, stress, positive and negative affect, and alexithymia were queried using validated questionnaires. We compared those dyspeptic patients who met Rome III criteria for FD to those who did not meet these criteria. KEY RESULTS: Two hundred and nine patients (160 female; mean age 46.6 years ± 17.3 years) participated. Around 151 patients (72%) met Rome III criteria for FD. In the entire group, a high level of depression, anxiety, somatization, and perceived stress was present compared to population norms. Health care seeking behavior and symptom severity were greater in those with FD and quality of life was lower compared to non-FD. Gastric emptying did not differentiate the two groups and similar degrees of psychological distress were present whether emptying was delayed or normal. CONCLUSIONS & INFERENCES: In patients referred for GET, substantial psychological distress is present. The degree of distress was similar regardless of whether the patient met Rome III FD criteria or not. Further evaluation of psychological dysfunction in FD patients may lead to improved diagnosis and determination of the most appropriate treatment.

The impact of obesity on oesophageal acid exposure time on and off proton pump inhibitor therapy.

BACKGROUND: Obesity is associated with increased oesophageal acid exposure time (AET) in patients with gastro-oesophageal reflux (GER), and may decrease the effects of proton pump inhibitors (PPIs). AIM: To evaluate the effects of increased body mass on the ability of PPI therapy to decrease AET in patients with reflux symptoms. METHODS: Acid exposure time profiles collected from adult patients using wireless pH-metry while on or off PPI therapy was retrospectively reviewed. Patients were separated into five body mass index (BMI) categories as defined by the World Health Organization. A multivariable logistic regression evaluated the association between abnormal AET and BMI groups while controlling for age, gender and pH capsule placement methods. RESULTS: The study group comprised 968 patients with 336 (34.7%) studied on a PPI and 632 (65.3%) studied off PPI therapy. AET (total greater than 5.3%) was found more frequently in the overweight (67%) and obese classes (74-80%) compared to those who were normal weight (40%) while off acid-suppressing medications (P < 0.001). No significant differences were found between these groups when studied on acid-suppressing medications, and the proportion of patients with abnormal AET across BMI classes was similar regardless of taking a PPI either once or twice daily. CONCLUSIONS: This is the largest study to report on the relationship between BMI and oesophageal acid exposure time in patients with GER on and off PPI therapy. We conclude that obesity is related to increased acid exposure time, but with no significant difference in acid exposure time among different weight-based groups when taking a once or twice-daily PPI.

Weak peristalsis with large breaks in chronic cough: association with poor esophageal clearance.

BACKGROUND: Gastroesophageal reflux plays an important role in chronic cough (CC). Whether disturbed esophageal motility contributes to increased esophageal reflux exposure or interferes with swallowed bolus clearance is unclear. This study used high resolution esophageal manometry and impedance (HRIM) together with Chicago Classification, and 24-h impedance pH (MII/pH) to address these questions in patients with CC compared with heartburn (HB). METHODS: A retrospective review of 32 patients with CC (mean age 57 [95% CI: 52-62] years) and 32 patients with symptoms of HB (55 [52-62] years) referred for HRIM and MII/pH between September 2012 and September 2013 was undertaken. KEY RESULTS: Weak peristalsis with large breaks (WPLBs) was observed in 34% of CC patients compared with only 12% of HB patients (p = 0.027). Pathological acid exposure time (AET) was identified in 81% of CC patients with WPLBs compared with 29% without (p = 0.011). Increased AET was associated with prolonged clearance time of refluxed events (p = 0.006) rather than increased number of events. AET correlated with the percentage of peristaltic events with large breaks in CC (ρ = 0.467, p = 0.007). Similar data were obtained for total bolus (acid and non-acid) exposure time. Only one of the CC patients with WPLBs exhibited complete bolus transit (CBT) on swallowing compared with 81% without WPLBs (p < 0.001). Moreover, the percentage of peristaltic events associated with CBT negatively correlated with the percentage of peristaltic events with large breaks (r = -0.653, p < 0.001) in CC. CONCLUSIONS & INFERENCES: One-third of CC patients exhibit WPLBs, which directly impacts on clearance of refluxed events and bolus's swallowed. These observations may have important implications for esophageal-bronchial interaction in CC.

Novel partial 5HT3 agonist pumosetrag reduces acid reflux events in uninvestigated GERD patients after a standard refluxogenic meal: a randomized, double-blind, placebo-controlled pharmacodynamic study.

BACKGROUND: Low basal lower esophageal sphincter (LES) pressure and transient LES relaxations are major causes of gastroesophageal reflux disease (GERD). Pumosetrag, a novel selective partial 5HT3 receptor agonist, showed a promising effect on reducing reflux events in health. We aimed to evaluate the effect of pumosetrag on changes in reflux episodes, lower esophageal sphincter pressure (LESP), and specific symptoms in patients with GERD receiving a refluxogenic meal. METHODS: Patients with GERD, who developed heartburn and/or regurgitation after ingestion of a refluxogenic meal, were randomized to 1 of 3 dose levels of pumosetrag (0.2, 0.5, or 0.8 mg) or placebo. Before and after 7 days of treatment, patients underwent manometry, intraesophageal multichannel, intraluminal impedance and pH after a standard refluxogenic meal. KEY RESULTS: A total of 223 patients with GERD [125 (56%) women, mean (SD) age = 36 (12) years] were enrolled. No overall treatment effects were detected for the total number of reflux episodes (acidic and weakly acidic) (p > 0.5); however, significant treatment effects (p < 0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2 mg (10.8 ± 1.1), 0.5 mg (9.5 ± 1.1), and 0.8 mg (9.9 ± 1.1) compared with placebo (13.3 ± 1.1). Significant treatment effects (p < 0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5 mg (10%) and 0.8 mg (10%) compared with placebo (16%). CONCLUSIONS & INFERENCES: In GERD, the partial 5HT3 agonist pumosetrag significantly reduced the rate of acid reflux events but did not result in a significant change in LESP or symptomatic improvement over a 1-week treatment period.

Long-term results of electrical stimulation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease.

BACKGROUND AND STUDY AIMS: In patients with gastroesophageal reflux disease (GERD), temporary electrical stimulation of the lower esophageal sphincter (LES) increases LES pressure without interference with LES relaxation. The aim of the current study was to investigate the safety and efficacy of long term LES electrical stimulation therapy (LES-EST), using a permanently implanted stimulator for the treatment of GERD. PATIENTS AND METHODS: Patients with GERD who were at least partially responsive to proton pump inhibitors (PPIs) and who had hiatal hernia of ≤ 3 cm and esophagitis of Los Angeles Grade A, B, or C were included in the study. Stimulation electrodes were placed in the LES and a pulse generator (EndoStim LES Stimulation System; EndoStim BV, The Hague, The Netherlands) was implanted laparoscopically. LES stimulation was delivered at 20 Hz, 215 µs, 3 - 8 mA in multiple 30-minute sessions. Patients were evaluated at follow-up using the GERD Health-Related Quality of Life (HRQL) questionnaire, daily symptom and medication diaries, the SF-12 Health Survey, esophageal pH testing, and high resolution manometry. RESULTS: A total of 24 patients (mean age 53 ± 12 years; 14 men) were implanted and 23 completed the 12-month evaluation. No serious implantation or stimulation-related adverse affects or sensations were reported. Median composite GERD-HRQL score at 12 months was 2.0 (interquartile range [IQR] 0 - 3.0), which was significantly better than baseline scores both on PPI therapy (median 9.0, IQR 6.0 - 10.0; P = 0.002) and off PPIs (median 23.5, IQR 21 - 25.75; P < 0.001). The median percentage of the 24-hour period with esophageal pH < 4.0 at baseline was 10.1 % (IQR 7.7 - 15.5), which was reduced to 3.3 % (1.8 - 6.9) at 12 months (P < 0.001), with 69 % of patients showing either normalization or > 50 % improvement in their distal esophageal pH. At 12 months, 96 % of patients (22/23) were completely off PPI medication. CONCLUSION: During the long term follow-up of 12 months, LES - EST was safe and effective for the treatment of GERD. There was a significant and sustained improvement in GERD symptoms, reduction in esophageal acid exposure with elimination of daily PPI usage, and no stimulation-related adverse effects.

Functional dyspepsia: the economic impact to patients.

BACKGROUND: Although highly prevalent, little is known about the economic impact of functional dyspepsia (FD). AIMS: To quantify FD patients' health care utilisation patterns and to estimate direct and indirect costs of FD to patients. METHODS: ICD-9 codes identified adult patients with dyspepsia. A validated questionnaire was mailed to patients who met Rome III criteria for FD. RESULTS: Three hundred and fifty-five patients met all inclusion criteria. The response rate was 63%. The respondents' mean age was 50 (14) years; 75% were women; 52% of respondents rated their FD as moderate. Patients reported 3 visits (mean) to their PCP over 12 months; 75% reported having blood work, 92% an EGD, 59% an ultrasound and 40% a CT scan. The direct cost of testing using Medicare reimbursement rates per patient was $582. To treat FD symptoms, 89% tried dietary changes, 89% over-the-counter medications, 87% prescription medications and 25% alternative therapies. Mean patient expenditure over the last year was $246 for OTC medications (range $0-12,000), $290 for co-payments (range $0-9,000) and $110 for alternative treatments (range $0-3,741). Total mean direct cost yearly to patients was $699. In the 7 days prior to completing the questionnaire, respondents reported a mean of 1.4 h absence from work. Extrapolating the results to the US population, we conservatively calculate the costs of FD were $18.4 billion in 2009. CONCLUSIONS: Functional dyspepsia patients incur significant direct and indirect costs and work productivity is impaired by dyspeptic symptoms.

Linaclotide in the management of gastrointestinal tract disorders.

Chronic constipation is a highly prevalent, heterogeneous disorder that significantly affects patients' lives. Nearly 15% of the U.S. population meets diagnostic criteria for chronic constipation (1). Chronic constipation reduces patients' quality of life and imposes a significant economic burden to the healthcare system (2, 3). A number of therapeutic options are currently available to treat symptoms of chronic constipation, although they are not universally successful (4, 5). Irritable bowel syndrome (IBS) is another common functional gastrointestinal disorder, with a prevalence rate estimated at up to 12% in the U.S. (6). Similar to chronic constipation, IBS imposes a significant impact on both the healthcare system and the individual patient (7-12). Currently, only one medication (lubiprostone) is approved by the U.S. Food and Drug Administration for the treatment of IBS with constipation (IBS-C), and is approved only for women (13). Although effective in many patients, it is not universally effective for the treatment of constipation symptoms in all patients with IBS-C. Other treatment options are therefore needed for those patients with chronic constipation and IBS-C who fail currently available therapies. This article will present information on the pharmacology and pharmacokinetics of linaclotide, a new agent designed to treat symptoms of both chronic constipation and IBS-C. Preclinical data, clinical studies and safety data will also be reviewed.

Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies.

UNLABELLED: Studies on use of selective serotonin reuptake inhibitors (SSRIs) and risk of fracture have yielded inconsistent results. This meta-analysis, which pooled results from 13 qualifying cohort and case-control studies, found that SSRIs were associated with a significantly increased risk of fractures. INTRODUCTION: This study was conducted to assess whether people who take SSRIs are at an increased risk of fracture. METHODS: We conducted a meta-analysis of observational studies. Relevant studies published by February 2010 were identified through literature searches using MEDLINE (from 1966), EMBASE (from 1988), PsycINFO (from 1806), and manual searching of reference lists. Only cohort or case-control studies that examined the association of SSRIs and risk of fracture and bone loss were included. Data were abstracted independently by two investigators using a standardized protocol; disagreements were resolved by consensus. Random effects models were used for pooled analysis due to heterogeneity in the studies. RESULTS: Thirteen studies met inclusion criteria. Overall, SSRI use was associated with a significantly increased risk of fracture (relative risk, RR, 1.72; 95% CI [1.51, 1.95]; P < 0.001). An increased fracture risk associated with SSRIs also was observed in the three studies that adjusted for bone mineral density (RR, 1.70; 95% CI [1.28, 2.25]; P < 0.001) and in the four studies that adjusted for depression (RR 1.74; 95% CI [1.28, 2.36]; P < 0.001). SSRI use was not associated with bone loss in the two cohort studies of women (P = 0.29). The overall association between SSRI use and fracture risk was weaker (RR, 1.40; 95% CI [1.22, 1.61]), though still significant (P < 0.001) in analyses that accounted for apparent publication bias. CONCLUSIONS: Use of SSRIs is associated with increased risk of fracture. The SSRIs may exert an increased risk of fracture independent of depression and bone mineral density.

The effects of intraduodenal nutrient infusion on serum CCK, LES pressure, and gastroesophageal reflux.

BACKGROUND: Fats cause reflux symptoms in many patients and cholecystokinin (CCK) may play a role. This study was designed to evaluate the effects of intraduodenal nutrient infusion on serum CCK levels, lower esophageal sphincter (LES) pressure, and gastroesophageal reflux (GER). METHODS: Twenty-four asymptomatic volunteers were studied. A Dent sleeve catheter assessed LES function while an impedance-pH catheter measured reflux events. Participants were randomized to fat (F), carbohydrate (C) or protein (P) infusion. Serum CCK and LES pressures were measured at baseline and after nutrient infusion. KEY RESULTS: Baseline LES pressures and CCK levels were similar in all three groups. A significant linear decrease was found in LES pressure during F, but not C or P, infusion (P=0.004). A significant interaction effect was noted between the infusion groups and CCK levels (P=0.002). A significant linear increase was noted in CCK levels during F but not during C or P infusion (P=0.02). A significant inverse correlation was found between CCK levels and LES pressure (ρ=-0.43; P=0.04). Esophageal acid exposure was significantly increased in the F infusion group (median; interquartile range: 1.10%; 0.25-4.7%) compared to both the C (0.03%; 0.00-0.39%) and P infusion (0.03%; 0.00-0.39%) groups (P=0.04). CONCLUSIONS & INFERENCES: Intraduodenal F infusion was associated with an increase in CCK levels, while P and C were not. LES pressure decreased significantly after fat infusion and reflux events were more frequent. Fat-induced CCK release is another mechanism that contributes to GER.

An economic analysis of endoscopic ablative therapy for management of nondysplastic Barrett's esophagus.

BACKGROUND AND AIMS: Advances have occurred in the development of safe and effective ablative therapies for Barrett's esophagus. The aim of the current study was to perform an economic analysis evaluating the cost-effectiveness of endoscopic ablation of nondysplastic Barrett's esophagus. METHODS: A Markov model evaluated three competing strategies in a hypothetical 50-year-old cohort with nondysplastic Barrett's esophagus from a societal perspective. Strategy I -- natural history of Barrett's disease (without surveillance); Strategy II -- surveillance performed according to the American College of Gastroenterology practice guidelines; Strategy III -- endoscopic ablative therapy. The model was biased against ablative therapy with a conservative estimate of complete response and continued standard surveillance even after complete ablation. All potential complications were accounted for, and an incomplete histological response after ablation was presumed to have the same risk of progression as untreated Barrett's. Transitional probabilities, discounted cost, and utility values to estimate quality-adjusted life-years (QALY) were obtained from published information. Direct costs were used in our analysis. RESULTS: In baseline analysis, the ablative strategy yielded the highest QALY and was more cost-effective than endoscopic surveillance. In a Monte Carlo analysis, the relative risk of developing cancer in the strategy based on endoscopic ablation was decreased compared with the other strategies. In threshold analysis, the critical determinants of cost-effectiveness of the ablative strategy were rate of complete response to ablation, total cost of ablation, and risk of progression to dysplasia. CONCLUSIONS: Within the limits of the model, ablation for nondysplastic Barrett's esophagus is more cost-effective than endoscopic surveillance. Clinical trials of ablative therapy in nondysplastic Barrett's esophagus are needed to establish its effectiveness in reducing cancer risk.

Observational study of the frequency of use and perceived usefulness of ancillary manoeuvres to facilitate colonoscopy completion.

BACKGROUND: A paucity of information exists regarding the frequency of use and usefulness of ancillary manoeuvres such as applying abdominal pressure and changing patient position to successfully complete colonoscopy. This information would be useful to understand and improve colonoscopy technique. AIM: We sought to determine the frequency, type and perceived success of ancillary manoeuvres used when performing colonoscopy during routine clinical practice. PATIENTS AND METHODS: A prospective, observational study was conducted at an outpatient endoscopy centre with a diverse group of colonoscopists. Our hypothesis was that ancillary manoeuvres would be used frequently by endoscopists of varying levels of experience and would be helpful in achieving successful caecal intubation. Information collected included patient and staff characteristics, procedural information and use of ancillary manoeuvres. Additional descriptive information was obtained when a manoeuvre was performed. RESULTS: One thousand three hundred and twenty-seven patients participated (691 women; mean age 62.5+/-12.3). The caecum was reached in 94% of cases. One or more ancillary manoeuvres were used in 73% of cases. Whilst one or two manoeuvres were helpful to achieve caecal intubation, increased manoeuvres were associated with an increased risk of incomplete colonoscopy. CONCLUSION: These data suggest that ancillary manoeuvres are used frequently but are not necessarily predictive of successful caecal intubation. Additional data from prospective, randomised studies are needed to address the overall utility and optimal application of individual manoeuvres.

Patient characteristics, clinical, endoscopic, and histologic findings in adult eosinophilic esophagitis: a case series and systematic review of the medical literature.

The objective of our study is to describe patient characteristics, clinical, endoscopic, and pathologic features and management of adult eosinophilic esophagitis (EE). A retrospective review of adults with EE (20 or more eosinophils per high-power field) diagnosed between 1997 and 2006, and a systematic review of the medical literature was performed. Forty-two patients (31 male; 11 female) had EE. Mean (SD) age at diagnosis was 44 (15.8) years, with highest prevalence (48%) at age 20-39. Predominant symptoms were dysphagia (81%); median duration, 8 years; range, 1-30 years and food impaction (55%). Forty-three percent had allergy or atopy, 36% had asthma, 54% had peripheral eosinophilia, and 10% had a first-degree relative with dysphagia. Endoscopic findings included ringed esophagus (55%), linear furrows (33%), narrow esophagus (10%), normal esophagus (7%), and esophageal strictures (38%). Mean number of dilations was 2 (range, 1-5). There were no perforations, but superficial mucosal tears occurred in 31% of dilations. Nine patients were treated with topical fluticasone with clinical improvement in all four (100%) patients who were seen in follow-up. Pathologic findings included 20 or more eosinophils per high-power field from proximal or mid-esophageal biopsy specimens. A systematic review of 14 studies (11 manuscripts, 2 abstracts, and this case series) with 212 patients showed similar findings. EE should be suspected in young men with unexplained dysphagia or food impaction even in the absence of typical endoscopic findings of rings or corrugations, linear furrows, and narrow esophagus; diagnosis is confirmed by 20 or more eosinophils per high-power field on proximal or mid-esophageal biopsies; EE is associated with allergic or atopic disorders; topical steroids are effective in the management of EE; dilation of esophageal strictures is reasonably safe in EE.