Cost of Constipation: A New Look With a Focus on New Medications.

GOAL: The study was designed to assess drug costs for constipation therapy and to relate costs to markers of functional status. BACKGROUND: Secretagogues have been introduced as new agents for the treatment of constipation. Previously published modeling studies suggested that improved productivity lowers the indirect disease burden and balances the higher drug costs. STUDY: Data were abstracted from the publicly available Medical Expenditure Panel Survey to identify adults with a functional gastrointestinal disorder who received a prescription for laxatives or secretagogues covering >2 days. Demographic data, recorded health care utilization and cost, and markers of functional status were extracted for the years from 2005 to 2017 to determine differences between participants treated with secretagogues or laxatives. RESULTS: The cohort of 2006 persons was female predominant [67.8%; age: 56.9 (55.8-57.9) years] and spent $92.89 (75.68-110.10) for medications treating constipation. The use of secretagogues (10.3% of the cohort) was the best independent predictor of constipation treatment costs. Using quality of life measures, perceived limitations in activities or work, and absenteeism, there was no difference between participants receiving laxatives and those taking secretagogues. CONCLUSION: Using survey data designed to be representative of the United States population, the study identified secretagogues as a key cost factor in drug treatment of constipation. The results do not support models suggesting improved role functioning offsets these higher direct expenditures. While prospective comparative studies are needed to more definitively correlate costs with direct or indirect benefits of different agents, limiting the use of more expensive medications to otherwise refractory cases may help to reign in the spiraling health care costs in this country.

Perceived Barriers to Treatment in Persons Treated for Functional Gastrointestinal Disease with Constipation.

INTRODUCTION: Despite expanding treatment options, patients with functional gastrointestinal disorders (FGID) frequently express concerns about problems with access to care. We hypothesized that health insurance coverage contributes to the perceived problems with care delivery. METHODS: Using the Medical Expenditure Panel Survey, we examined a cohort of participants defined by the diagnosis code for FGID plus the recorded prescription for laxative therapy. Demographic data, healthcare utilization and cost, insurance coverage, comorbid conditions, and information about provider characteristics were extracted for the years 2005-2015. Age- and sex-matched controls were identified for each year included. Barriers to care were based on responses to questions about inability to receive timely care or medication. Logistic regression was used to identify independent predictors of perceived barriers. RESULTS: The cohort was female predominant (67.8%; mean age: 58.8 ± 0.33 years) with 15.4% reporting problems with access to care. Limited insurance coverage was most commonly cited by respondents. Consistent with this result, uninsured persons were significantly more likely to report barriers to care, while the type of insurance for those covered did not independently predict access problems. In addition, comorbidity burden and provider-specific factors, such as available contact options or insufficient explanations, correlated with perceived barriers to care delivery. CONCLUSION: While the study design cannot establish causal links, persons with FGID commonly report access problems, which correlate with lack of health insurance and comorbidities. Providers can influence this perception by offering more flexible office hours and incorporating patient expectations related to treatment explanations and shared decision-making.

Impact of Health Insurance, Poverty, and Comorbidities on Colorectal Cancer Screening: Insights from the Medical Expenditure Panel Survey.

BACKGROUND: Despite national campaigns and other efforts to improve colorectal cancer (CRC) screening, participation rates remain below targets set by expert panels. We hypothesized that availability and practice patterns of healthcare providers may contribute to this gap. METHOD: Using data of the Medical Expenditure Panel Survey for the years between 2000 and 2016, we extracted demographic, socioeconomic, and health-related data as well as reported experiences about barriers to care, correlating results with answers about recent participation in colorectal cancer screening. As CRC screening guidelines recommend initiation of testing at age 50, we focused on adults 50 years or older. RESULTS: We included responses of 163,564 participants for the period studied. There was a significant increase in CRC screening rates over time. Comorbidity burden, poverty, race, and ethnicity independently predicted participation in screening. Lack of insurance coverage and cost of care played an important role as reported barrier. Convenient access to care, represented by availability of appointments beyond typical business hours, and frequency of provider interactions, correlated with higher rates of screening. CONCLUSION: Our data show a positive effect of educational efforts and healthcare reform with coverage of screening. Easy and more frequent access to individual providers predicted a higher likelihood of completed screening tests. This finding could translate into more widespread implementation of screening programs, as the increasingly common virtual care delivery offers a new and convenient option to patients.

Time Trends in Healthcare Utilization Due to Self-Reported Functional Diseases of the Stomach.

INTRODUCTION: Cohort studies from referral centers suggest an increasing burden of functional gastric disorders, with frequent emergency room (ER) visits, hospitalizations, or absenteeism. We hypothesized that recruitment from tertiary care sites skews results and thus investigated the burden of these illnesses, using the population-based data of the Medical Expenditure Panel Survey (MEPS). METHODS: Using MEPS data for the years 2000-2015, demographic, economic, healthcare-related, and quality-of-life indicators were extracted for adults reporting the diagnosis of functional gastric diseases to assess trends and to compare results with data from all adults surveyed. RESULTS: Between 2000 and 2015, 2.7 ± 0.2% of the adults surveyed reported a functional gastric illness. Within the period studied, 28.8 ± 2.8% and 17.9 ± 1.6% of this cohort reported ER visits or hospitalizations, respectively. Only a fraction of these persons attributed the ER visits (22.6 ± 0.9%) or admissions (10.9 ± 0.8%) to the functional gastric disorder. Rates remained stable rates during the period studied. Female sex, measures of physical function, comorbidities, and an income below the poverty line were predictors of healthcare utilization. While utilization was stable over time, annual costs increased by 113.9 ± 16.6% during the study period, outpacing the inflation rate of 37.6%. CONCLUSIONS: Persons with functional gastric disorders have significant healthcare needs and face increasing costs of care, largely due to coexisting illnesses. While it is important to recognize this impact, the need for emergency care or hospitalizations remained stable and lower than reported for patients seen in tertiary referral centers, providing reassuring information for patients and providers.

Unrelated Death After Colorectal Cancer Screening: Implications for Improving Colonoscopy Referrals.

The observed mortality < 5 years after the index colonoscopy lowered the overall impact of screening, which should prompt health care providers to perform a more thorough assessment of the potential reduced benefit for individual veterans when incorporating cancer risk, comorbidity burden, and age-based criteria.

Pharmacological Treatment of Opioid-Induced Constipation Is Effective but Choice of Endpoints Affects the Therapeutic Gain.

BACKGROUND: Widespread opioid use has led to increase in opioid-related adverse effects like constipation. We examined the impact of study endpoints on reported treatment benefits. METHODS: Using MEDLINE, EMBASE, and ClinicalTrials.gov, we searched for randomized control trials targeting chronic opioid-induced constipation (OIC) and subjected them to meta-analysis. Data are given with 95% confidence intervals. RESULTS: Thirty trials met our inclusion criteria. Combining all dichotomous definitions of responders, active drugs were consistently more effective than placebo, with an odds ratio (OR): 2.30 [2.01-2.63; 15 studies], independent of the underlying drug mechanism. The choice of endpoints significantly affected the therapeutic gain. When time from drug administration to defecation was used, the OR decreased from 4.74 [2.71-4.74] at 6 h or less to 2.46 [1.80-3.30] at 24 h (P < 0.05). Using other response definitions, the relative benefit over placebo was 2.10 [1.77-2.50; 12 studies] for weekly bowel frequency, 2.03 [1.39-2.95; 9 studies] for symptom scores, 2.21 [1.25-3.90; 4 studies] for global assessment scales, and 1.27 [0.79-2.03; 7 studies] for rescue laxative use. CONCLUSION: While treatment of OIC with active drugs is more effective than placebo, the relative gain depends on the choice of endpoints. The commonly used time-dependent response definition is associated with the highest response rate but is of questionable relevance in a chronic disorder. The limited data do not clearly demonstrate a unique advantage of the peripherally restricted opioid antagonists, suggesting that treatment with often cheaper agents should be optimized before shifting to these novel expensive agents.

Glass half empty? Lessons learned about gastroparesis.

Gastroparesis is defined as a combination of chronic dyspeptic symptoms and delayed emptying of a solid test meal. It remains a difficult-to-treat disorder with a significant impact on quality of life. Although gastroparesis is defined by delayed emptying, several important studies did not find a correlation between this biomarker and symptom severity or treatment success. Thus, some of the more recent trials explored strategies that ranged from antiemetics to antidepressants. Although dietary management showed benefit, most of the other interventions were barely superior to placebo or were not superior at all. Placebo responses were often quite high and this complicates the assessment of active agents. While it complicates the design and interpretation of clinical trials, high response rates for active and sham interventions indicate that we can achieve symptom relief in many patients and thus give them some reassurance. If indeed most therapies are only marginally better than placebo, the differences in adverse effects should be weighed more strongly, a point that is especially important in view of the controversy surrounding metoclopramide. Mechanistic studies introduced the network of macrophages as another potentially important player in the development of gastroparesis. Results are too preliminary and are largely based on preclinical data but show up- and downregulation of cellular elements controlling gastric function. Thus, future developments may teach us how they interfere with some of these mechanisms in clinical settings, potentially making gastroparesis a reversible process.

Prevalence of Nausea and Vomiting in Adults Using Ropinirole: A Systematic Review and Meta-Analysis.

BACKGROUND: Nausea and vomiting are commonly associated with medication use. Dopaminergic agonists have been associated with these symptoms, but their impact in patients without Parkinson's disease, such as those with restless legs syndrome (RLS), is not well characterized. AIMS: We sought to determine whether the non-ergoline dopamine agonist ropinirole is associated with nausea and vomiting in adults with RLS. METHODS: We conducted a systematic review using PUBMED, EMBASE, and clinical trial databases to identify placebo-controlled clinical trials of ropinirole for RLS treatment. We extracted data including dosing schedule and the proportion of patients reporting nausea and/or vomiting. We also determined hazard ratios (HR) using a random effects proportional hazard model. RESULTS: We extracted data from a pool of 13 studies. The prevalence of nausea in the ropinirole-treated RLS group (RLS-R; N = 1528) was 37.2% compared to 9.4% in the placebo-treated RLS group (RLS-P; N = 1395) (p < 0.0001). The prevalence of vomiting in the RLS-R group was 10.9% compared to 2.6% in the RLS-P group (p < 0.0001). Ropinirole use was associated with a higher risk of reporting nausea (HR 5.924 [4.410-7.959], p < 0.001) and experiencing vomiting (HR 4.628 [3.035-7.057], p < 0.0001). Nausea and vomiting represented nearly 50% of all adverse events reported. CONCLUSIONS: Nausea and vomiting are quite common side effects in those using ropinirole for RLS. As RLS is more widely recognized and treated; the prevalence of ropinirole-induced nausea and vomiting could grow substantially. Ropinirole use should be considered as a cause of chronic nausea and vomiting.

Risk of Pancreatitis Following Treatment of Irritable Bowel Syndrome With Eluxadoline.

BACKGROUND & AIMS: The Food and Drug Administration approved eluxadoline for the treatment of diarrhea-predominant irritable bowel syndrome despite cases of pancreatitis in early stage trials. We investigated the frequency of pancreatitis attributed to eluxadoline in postmarketing surveillance. METHODS: We extracted reports on eluxadoline submitted to the Federal Adverse Event Reporting System from January through September 2016. We collected data on patient age and sex, event date, reporting entity (consumer, physician, pharmacist, legal worker, or other), medications, dosages, presumed role in the event (coinciding, primary, or secondary suspect), treatment indication, and outcome (death, life threatening, hospitalization, disability, or other).We compared data for eluxadoline with data from antidiarrheals, oxycodone, and rifaximin using the κ2 test, Kruskal-Wallis rank test, and analysis of variance; findings with P < .05 were considered statistically significant. RESULTS: Pancreatitis accounted for 16.4% of the 597 reports of adverse events linked to eluxadoline; 53 cases required hospitalization. Pancreatitis was listed as treatment complication of other agents in significantly lower proportions of cases (loperamide, 0.3%; diphenoxylate, 0.4%; oxycodone, 0.2%; rifaximin, 0.5%), with 75% of these submissions not considering the agent as causal. CONCLUSIONS: In an analysis of reports on eluxadoline submitted to the Federal Adverse Event Reporting System, we confirmed a previously reported risk of pancreatitis associated with eluxadoline. The need for hospitalization in at least half of these instances and a recent report of 2 fatalities should prompt reassessments of the agent's risk-benefit ratio.

Assessment of Pharmaceutical Company and Device Manufacturer Payments to Gastroenterologists and Their Participation in Clinical Practice Guideline Panels.

Importance: Payments from pharmaceutical and device manufacturers to physicians may influence the advice physicians give patients and peers. Objectives: To investigate the nature and amounts of monetary and other benefits that gastroenterologists received and to determine the participation of those receiving benefits in the formulation of clinical practice guidelines. Design, Setting, and Participants: This cohort study analyzed information from the Centers for Medicare & Medicaid Services Open Payments database, including all reports about payments that pharmaceutical and device manufacturers gave to adult or pediatric gastroenterologists in 2016. PubMed was used to examine the professional affiliations and publication records of top payment recipients. Panelists of clinical guidelines who also received personal financial rewards listed in the Open Payments database were identified. Main Outcomes and Measures: Payments made to gastroenterologists by pharmaceutical company and device manufacturers. Results: Of 15 497 gastroenterologists, 13 467 (86.9%) received a total of 432 463 payments accounting for a total expenditure of $67 144 862. Direct financial payments for consultations, talks, or other services were made to 2055 physicians and were responsible for 4.2% of payments (18 179 of 432 463), but for 62.7% of total expenditures ($42 086 207 of $67 144 862). Although a significant number of submissions were for food and beverages, they constituted only a small amount of total expenditure. For gastroenterologists treating adult patients, 10 products were linked to 63.8% of payments (11 221 of 17 588) related to direct financial rewards and 37.1% of the total expenditures ($24 892 643 of $67 144 862). Twenty-nine of 36 clinical practice guidelines included panelists who had received honoraria or consultation fees from industry sources, with amounts exceeding $10 000 in 8 of them (22%). Conclusions and Relevance: Most gastroenterologists accept meals or gifts from industry, with 2055 of 15 497 gastroenterologists receiving direct payments and 8 of 36 clinical practice guidelines panelists having received more than $10 000. Considering the known impact of such benefits on prescribing patterns and other professional behaviors, policy makers should consider revising regulations governing interactions with industry and disclosure formats alerting others to their potential biasing impact.

Expanding the Scope of Telemedicine in Gastroenterology.

A specialty outreach program relied on telemedicine to reach patients with gastrointestinal and liver diseases in a large service area.

Risk factors for hospitalizations among patients with cirrhosis: A prospective cohort study.

This study was designed to assess unique baseline factors associated with subsequent hospitalizations in a cohort of outpatients with cirrhosis. A cohort of 193 patients with cirrhosis was recruited from an outpatient liver disease clinic at a single, tertiary medical center. Comorbidities, prescription medications, liver disease symptoms and severity, and psychiatric and pain symptoms were assessed at baseline using validated instruments. Inflammatory markers were measured using standardized Luminex assays. Subsequent hospitalizations and the primary admission diagnoses were collected via chart review. Multivariable models were used to evaluate which baseline factors were associated with time to hospitalization and number of hospitalizations. The cohort consisted of 193 outpatients, with an average age of 58±9 and model for end-stage liver disease (MELD) score of 12±5. Over follow-up, 57 (30%) were admitted to the hospital. The factors associated with time to hospitalization included the severity of liver disease (HR/MELD point:1.10, 95% CI:1.04,1.16), ascites (HR: 1.90, 95% CI: 1.01, 3.58), baseline symptoms of depression (HR:2.34, 95% CI:1.28,4.25), sleep medications (HR:1.81, 95% CI:1.01, 3.22) and IL-6 (HR:1.43, 95% CI: 1.10, 1.84). Similarly the number admissions was significantly associated with MELD (IIR: 1.08, CI: 1.07,1.09), ascites (IIR: 4.15, CI:3.89, 4.43), depressive symptoms (IIR:1.54, CI:1.44,1.64), IL-6 (IIR:1.26, CI:1.23,1.30), sleep medications (IIR:2.74, CI:2.57, 2.93), and widespread pain (IIR: 1.61, CI: 1.50, 1.73). In conclusion, consistent with prior studies, MELD and ascites were associated with subsequent hospitalization. However, this study also identified other factors associated with hospitalization including inflammation, depressive symptoms, sleep medication use, and pain.

From Harmful Treatment to Secondary Gain: Adverse Event Reporting in Dyspepsia and Gastroparesis.

INTRODUCTION: Medical management of gastroparesis and functional dyspepsia remains difficult with several recent trials showing limited or no benefit. If treatment comes with only marginal improvements, concerns about adverse events become more relevant. We therefore examined the type and outcomes of side effects submitted to a public repository. METHODS: We searched the Federal Adverse Event Reporting System for reports associated with the treatment of dyspepsia or gastroparesis. Demographic data, medications used and implicated, side effects, and outcomes were abstracted for the years 2004-2015. RESULTS: Acid-suppressive agents and prokinetics were the most commonly listed medications with a stronger emphasis on prokinetics in gastroparesis. Submissions related to metoclopramide by far exceeded reports about other agents and mostly described tardive dyskinesia or other neurological concerns. They peaked around 2012, driven by submissions through legal workers. Most reports about metoclopramide described short-term use to prevent or treat nausea and vomiting. Concerns about acid-suppressive medications increased over time and spanned a wide spectrum of potential problems, including osteoporosis, worsening renal function, or cardiac events. CONCLUSION: Despite biasing factors, such as pending legal action, the voluntary repository of adverse events provides insight into current medical practice and its associated risk. Knowing about common and uncommon, but potentially serious risks may enable patients and providers to decide on effective and safe management strategies.

Adverse events of gastric electrical stimulators recorded in the Manufacturer and User Device Experience (MAUDE) Registry.

The role of gastric electrical stimulation for patients with refractory symptoms of gastroparesis remains controversial. Open label studies suggest benefit while randomized controlled trials did not demonstrate differences between active and sham intervention. Using a voluntary reporting system of the Federal Drug Administration, we examined the type and frequency of adverse events. METHODS: We conducted an electronic search of the Manufacturer and User Device Experience (MAUDE) databank using the keyword 'Enterra' for the time between January of 2001 and October of 2015. We abstracted information about the year of stimulator implantation, the year and type of adverse effect, the resulting intervention and outcome if available. RESULTS: A total of 1587 entries described adverse effects related the GES. Only 36 of the reports listed perioperative complications. The vast majority described problems that could be classified as patient concerns, local complications, or system failure. The most common problem related lack or loss of efficacy, followed by pain or complications affecting the pocket site. A subset of 801 reports provided information about the time between system implant and registration of concerns, which gradually declined over time. More than one third (35.7%) of the reported adverse events prompted surgical correction. CONCLUSION: The number of voluntarily reported adverse events and the high likelihood of repeated surgical interventions clearly demonstrate the potential downside of gastric electrical stimulation. Physicians considering this intervention will need to carefully weigh these risks and include this information when counseling or consenting patients.

Pre-Transplant Depression Is Associated with Length of Hospitalization, Discharge Disposition, and Survival after Liver Transplantation.

Depression after liver transplantation has been associated with decreased survival, but the effects of pre-transplant depression on early and late post-transplant outcomes remain incompletely evaluated. We assessed all patients who had undergone single-organ liver transplantation at a single center over the prior 10 years. A diagnosis of pre-transplant depression, covariates, and the outcomes of interest were extracted from the electronic medical record. Potential covariates included demographics, etiology and severity of liver disease, comorbidities, donor age, graft type, immunosuppression, and ischemic times. In multivariable models adjusting for these factors, we evaluated the effect of pre-transplant depression on transplant length of stay (LOS), discharge disposition (home vs. facility) and long-term survival. Among 1115 transplant recipients with a median follow-up time of 5 years, the average age was 56±11 and MELD was 12±9. Nineteen percent of the study population had a history of pre-transplant depression. Pre-transplant depression was associated with longer LOS (median = 19 vs. 14 days, IRR = 1.25, CI = 1.13,1.39), discharge to a facility (36% vs. 25%, OR 1.70,CI = 1.18,2.45), and decreased survival (HR = 1.54,CI = 1.14,2.08) in this cohort, accounting for other potential confounders. In conclusion, pre-transplant depression was significantly associated with longer transplant length of stay, discharge to a facility, and mortality in this cohort.

Physiology of Visceral Pain.

Pain involving thoracic, abdominal, or pelvic organs is a common cause for physician consultations, including one-third of chronic pain patients who report that visceral organs contribute to their suffering. Chronic visceral pain conditions are typically difficult to manage effectively, largely because visceral sensory mechanisms and factors that contribute to the pathogenesis of visceral pain are poorly understood. Mechanistic understanding is particularly problematic in "functional" visceral diseases where there is no apparent pathology and pain typically is the principal complaint. We review here the anatomical organization of the visceral sensory innervation that distinguishes the viscera from innervation of all other tissues in the body. The viscera are innervated by two nerves that share overlapping functions, but also possess notably distinct functions. Additionally, the visceral innervation is sparse relative to the sensory innervation of other tissues. Accordingly, visceral sensations tend to be diffuse in character, are typically referred to nonvisceral somatic structures and thus are difficult to localize. Early arguments about whether the viscera were innervated ("sensate") and later, whether innervated by nociceptors, were resolved by advances reviewed here in the anatomical and functional attributes of receptive endings in viscera that contribute to visceral pain (i.e., visceral nociceptors). Importantly, the contribution of plasticity (i.e., sensitization) of peripheral and central visceral nociceptive mechanisms is considered in the context of persistent, chronic visceral pain conditions. The review concludes with an overview of the functional anatomy of visceral pain processing. © 2016 American Physiological Society. Compr Physiol 6:1609-1633, 2016.

Disorders of gastrointestinal hypomotility.

Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases.

Association between opioid use and readmission following liver transplantation.

The aim of this study was to assess the independent association between pre-transplant prescription opioid use and readmission following liver transplantation. We reviewed the medical records of all patients at a single medical center undergoing primary, single-organ, liver transplantation from 2004 to 2014. We assessed factors associated with hospital readmission 30 days and 1 year after hospital discharge using multivariable competing risk regression models. Among 1056 transplant recipients, 49 (4.6%) were prescribed pre-transplant prescription opioids. Readmission occurred in 421 (40%) patients within 30 days and 689 (65%) within 1 year. Patients with pre-transplant opioid use had a significantly higher risk of readmission at 30 days (HR 1.7; 95% CI 1.1-2.5) and a non-significantly elevated risk at 1 year (HR 1.4; 95% CI 1.0-1.9) when controlling for other potential confounders. Although pain was the major reason for readmission in only 12 (3%) patients at 30 days and 33 (6%) patients at 1 year, pre-transplant opioid use was significantly associated with pain-related readmission at both time points. In conclusion, prescription opioid use pre-transplantation was significantly associated with all-cause 30-day readmissions and pain-related readmissions at 30 days and 1 year.

Adverse events of sacral neuromodulation for fecal incontinence reported to the federal drug administration.

AIM: To investigate the nature and severity of AE related to sacral neurostimulation (SNS). METHODS: Based on Pubmed and Embase searches, we identified published trials and case series of SNS for fecal incontinence (FI) and extracted data on adverse events, requiring an active intervention. Those problems were operationally defined as infection, device removal explant or need for lead and/or generator replacement. In addition, we analyzed the Manufacturer and User Device Experience registry of the Federal Drug Administration for the months of August - October of 2015. Events were included if the report specifically mentioned gastrointestinal (GI), bowel and FI as indication and if the narrative did not focus on bladder symptoms. The classification, reporter, the date of the recorded complaint, time between initial implant and report, the type of AE, steps taken and outcome were extracted from the report. In cases of device removal or replacement, we looked for confirmatory comments by healthcare providers or the manufacturer. RESULTS: Published studies reported adverse events and reoperation rates for 1954 patients, followed for 27 (1-117) mo. Reoperation rates were 18.6% (14.2-23.9) with device explants accounting for 10.0% (7.8-12.7) of secondary surgeries; rates of device replacement or explant or pocket site and electrode revisions increased with longer follow up. During the period examined, the FDA received 1684 reports of AE related to SNS with FI or GI listed as indication. A total of 652 reports met the inclusion criteria, with 52.7% specifically listing FI. Lack or loss of benefit (48.9%), pain or dysesthesia (27.8%) and complication at the generator implantation site (8.7%) were most commonly listed. Complaints led to secondary surgeries in 29.7% of the AE. Reoperations were performed to explant (38.2%) or replace (46.5%) the device or a lead, or revise the generator pocket (14.6%). Conservative management changes mostly involved changes in stimulation parameters (44.5%), which successfully addressed concerns in 35.2% of cases that included information about treatment results. CONCLUSION: With reoperation rates around 20%, physicians need to fully disclose the high likelihood of complications and secondary interventions and exhaust non-invasive treatments, including transcutaneous stimulation paradigms.

Empirically Supported Use of Psychiatric Medications in Adolescents and Adults with IBD.

BACKGROUND: The use of psychotropic medications, particularly antidepressants, is common in patients with inflammatory bowel disease (IBD) in spite of a lack of their robust efficacy in this population. This review provides an overview of the use trends of different classes of antidepressant and anti-anxiety medication and their effects on mood, nervous system function, gastrointestinal physiology and immunity drawing from the literature available in the general population, other medical conditions, and when available, patients with IBD. It also covers the evidence base for the actions, efficacy, and potential complications of antidepressants organized by different classes. METHODS: We conducted a PubMed search of articles relating the different drug classes probed to the terms above in different populations of interest. All types of articles were accepted including case reports and series, open and randomized trials, reviews, and expert opinion. We also examined the reference lists of the publications found. RESULTS: Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are the most commonly prescribed agents for anxiety and depression in patients with IBD, though their efficacy for these conditions in the general population are mild to moderate at best. SSRIs are generally well tolerated, though at higher doses, they, like most antidepressant classes, can be associated with activation, serotonergic syndrome, and increased suicidal ideation. TCAs have many more serious side effects but have some shown efficacy for functional GI symptoms. A newer class, the serotonin noradrenergic reuptake inhibitors (SNRIs), can be effective for refractory depression, anxiety and chronic pain syndromes with a side effect profile similar to both SSRIs and more mild manifestations of TCAs. Mirtazapine has moderate efficacy for depression if sedation and weight gain side effects are tolerated and some small support for use in nausea and vomiting. Bupropion targets dopamine and noradrenaline reuptake and has moderate efficacy for depression, and some small support for use in fatigue and smoking cessation. Buspirone has an indication for generalized anxiety disorder though studies show only a minimal benefit. It has some growing evidence for use in functional dyspepsia. Most of these agents have physiological effects on the brain, immune system, and gastrointestinal tract (with the exception of bupropion) hence their therapeutic and side effects manifested in these systems. CONCLUSION: Antidepressant medications are frequently prescribed for depression, anxiety disorders, and chronic pain syndromes, but overall support for their efficacy is modest at best. Psychological interventions have growing support for having much more robust effects without the side effects of antidepressants and should be considered first-line treatment or at least an adjunct to psychotropic medications for these conditions.