Citations

Background: Irritable bowel syndrome (IBS) reduces quality of life and burdens healthcare systems. This study identified factors associated with frequent use of IBS diagnostic tests and procedures. Methods: Using a United States claims database (2001–2012), tests and procedures in IBS patients occurring in the 2-year study period (12 months before/following the first IBS diagnosis) were analyzed: endoscopy, GI transit testing, anorectal procedures, and radiologic imaging. Patients were classified based on test/procedure frequency (3+, 1–2, or 0). Multivariate logistic regression identified factors associated with more frequent tests/procedures. Results: Among 201,322 IBS patients, 41.7% had 3+ tests/procedures, 35.1% had 1–2, and 23.3% had 0. Patients with more tests/procedures were older [mean age 50.6 (3+ group), more likely to be female and had more comorbidities, including anxiety, depressive disorders, and somatization. Dyspepsia [odds ratio (95% confidence interval): 1.80 (1.72–1.87)], interstitial cystitis [1.60 (1.45–1.77)], gastroesophageal reflux disease [1.59 (1.55–1.63)], constipation [1.50 (1.45–1.54)], and dyspareunia [1.38 (1.25–1.52)] were significantly associated with more tests/procedures (3+ versus 1–2), while anxiety, depressive disorders, and somatization were not. Patients with more frequent specialist visits [emergency department (ED; 1.10 (1.09–1.11)) and gastroenterologists (1.26 (1.26–1.27))] or at least one GI-related ED visit or inpatient admission [1.95 (1.86–2.04) and 3.67 (3.48–3.87), respectively] were more likely to have more tests/procedures (all p < 0.05). Conclusions: Test frequency in patients with IBS is strongly associated with demographic and clinical characteristics, especially comorbid conditions related to IBS. Presence of common overlapping comorbid conditions should increase clinicians’ confidence in making the diagnosis of IBS, thus curtailing redundant testing and reducing healthcare costs.

AbstractTrisomies of odd numbered chromosomes are seen in nearly half of patients with multiple myeloma (MM) and typically correlate with a hyperdiploid state and better overall survival (OS). We compared DNA ploidy of monoclonal plasma cells (as a surrogate for the presence of trisomies) assessed simultaneously by PCPRO (plasma cell proliferative index), a novel method that estimates DNA index by multi‐parametric flow cytometry to fluorescence in situ hybridization (FISH) in 1703 patients with plasma cell disorders. The distribution of ploidy was hyperdiploid: 759 (45%), diploid 765 (45%), hypodiploid: 71 (4%), tetraploid/near‐tetraploid: 108 (6%). FISH identified trisomies in 82% (621/756) of patients with hyperdiploidy by PCPRO and no trisomy by FISH was observed in 88% (730/834) of patients without hyperdiploidy. 95% (795/834) of patients without hyperdiploidy on PCPRO had one or less trisomy by FISH. Sensitivity and specificity of PCPRO for detecting hyperdiploidy was 86% (621/725) and 84% (730/865), respectively. Sensitivity increased to 94% (579/618) for patients with more than one trisomy. Newly diagnosed MM patients with hyperdiploidy on PCPRO (147/275) had better OS compared to nonhyperdiploid patients (median not reached vs 59 months, P = 0.008) and better progression free survival (median: 33 vs 23 months, P = 0.03). Within the hyperdiploidy group, patients with high‐hyperdiploidy (DNA index: 1.19‐1.50) versus those with low‐hyperdiploidy (DNA index: 1.05‐1.18) had superior OS (3 year OS of 88% vs 68% P = 0.03). Ploidy assessment by flow cytometry can provide rapid, valuable prognostic information and also reduces the number of copy number FISH probes required and hence the cost of FISH.

Abstract Peripheral blood biomarkers of tumor microenvironment and immune surveillance are independent prognostic factors in multiple myeloma. The timing and prognostic impact of immune reconstitution has been studied after autologous hematopoietic stem cell transplantation, less is known about its significance in newly diagnosed multiple myeloma. We studied absolute lymphocyte (ALC) and absolute monocyte (AMC) counts at the time of treatment initiation and 1 month thereafter in 771 newly diagnosed patients. Two hundred and thirty‐four patients (31%) had evidence of immune dysregulation at baseline (abnormal biomarkers). Eighty‐seven of these patients (37%) recovered normal biomarkers at 1 month (early immune reconstitution). The absence of immune dysregulation at baseline (compared to the presence thereof) was associated with better overall survival (HR 0.77, 95% CI 0.61‐0.97, P = 0.025, n = 771). The absence of immune dysregulation at 1 month (compared to the persistence or development thereof) was associated with better overall survival (HR 0.63, 95% CI 0.50‐0.80, P < 0.001, n = 771). Early immune reconstitution (compared to the persistence or development of immune dysregulation) was associated with better overall survival (HR 0.62, 95% CI 0.43‐0.92, P = 0.016, n = 771). Cytogenetic high‐risk disease was negatively, and treatment with immunomodulators positively, associated with early immune reconstitution. The presence or development of immune dysregulation in newly diagnosed multiple myeloma is an independent risk factor. The favorable impact of early immune reconstitution suggests immune dysregulation to be a potentially modifiable risk factor that may be exploited for therapeutic benefit.

Abstract The plasma cell proliferative index (PCPI), determined by a slide technique or by flow cytometry, detects cells in the S phase of the cell cycle and is a useful prognostic tool in patients with plasma cell disorders such as multiple myeloma and amyloidosis. We conducted a retrospective review analyzing the prognostic effect of PCPI in 306 patients with smoldering multiple myeloma (SMM). Seventy-nine (26%) patients had an elevated PCPI (&gt;0.5). An elevated PCPI predicted an inferior time to progression (median, 3.0 vs 7.1 years for those with a low PCPI; P = .0004). Within 24 months, the progression rate was significantly higher for patients with an elevated PCPI (49% vs. 20%; P &lt; .0001). PCPI is a valuable tool in risk stratifying patients with SMM and identifies patients with earlier progression who may benefit from closer follow-up and consideration of early intervention trials.

OBJECTIVES: Prokinetics are recommended for the treatment of functional dyspepsia (FD) but systematic reviews give conflicting results on the efficacy of these agents. We have therefore conducted an updated systematic review to support the 2017 joint ACG/CAG dyspepsia guidelines. METHODS: Electronic databases, including MEDLINE, EMBASE, and CENTRAL, were searched until September 2017 for randomized controlled trials (RCTs) comparing either prokinetics and placebo or two types of prokinetics to improve FD symptoms. The primary outcome was absence or improvement of dyspeptic symptoms at the end of treatment. Double-blind eligibility assessment and data extraction was performed. Pooled risk ratios of symptoms persisting or adverse events occurring, and standardized mean difference of quality-of-life (QoL) scores with 95% CI, using a random effects model, were calculated. Quality of evidence was assessed using GRADE. RESULTS: The search identified 1388 citations; 38 studies in 35 papers were included. Of these, 29 trials comparing prokinetics with placebo were found. There was a statistically significant effect of prokinetic treatment in reducing global symptoms of FD (RR 0.81, 95% CI 0.74 to 0.89; I 2 91%; NNT 7), regardless of FD subtype or ethnicity. When comparing two types of prokinetic, the most commonly used comparator was domperidone. There was no difference in reducing global symptoms (RR 0.94, 95% CI 0.83 to 1.07). QoL was not improved with prokinetic treatment. The adverse events with individual prokinetics were not different from placebo, except for cisapride. The GRADE assessment rated the quality of the evidence in each outcome as very low. CONCLUSIONS: From the current evidence, prokinetics may be effective for the treatment in all subtypes of FD, with very low quality of evidence. There was no difference between prokinetics for dyspeptic symptom improvement. High-quality RCTs with large sample sizes of FD patients are needed to verify the efficacy of prokinetics.

Summary Background Irritable bowel syndrome ( IBS ) is a chronic functional bowel disorder. Disturbances in the gastrointestinal microbiome may be involved in its aetiology. Aim To perform a systematic review and meta‐analysis to examine the efficacy of prebiotics, probiotics, synbiotics and antibiotics in IBS . Methods MEDLINE , EMBASE , and the Cochrane Controlled Trials Register were searched (up to July 2017). Randomised controlled trials ( RCT s) recruiting adults with IBS , comparing prebiotics, probiotics, synbiotics or antibiotics with placebo or no therapy were eligible. Dichotomous symptom data were pooled to obtain a relative risk ( RR ) of remaining symptomatic after therapy, with a 95% confidence interval ( CI ). Continuous data were pooled using a standardised mean difference with a 95% CI . Results The search identified 4017 citations. Data for prebiotics and synbiotics were sparse. Fifty‐three RCT s of probiotics, involving 5545 patients, were eligible. Particular combinations of probiotics, or specific species and strains, appeared to have beneficial effects on global IBS symptoms and abdominal pain, but it was not possible to draw definitive conclusions about their efficacy. There were five trials of similar design that used rifaximin in non‐constipated IBS patients, which was more effective than placebo ( RR of symptoms persisting = 0.84; 95% CI 0.79‐0.90). Adverse events were no more common with probiotics or antibiotics. Conclusions Which particular combination, species or strains of probiotics are effective for IBS remains, for the most part, unclear. Rifaximin has modest efficacy in improving symptoms in non‐constipated IBS .

AbstractPositron emission tomography‐computed tomography (PET‐CT) can identify bony lesions, assess disease burden, and detect extramedullary disease (EMD) in patients with multiple myeloma. We retrospectively reviewed records of patients who underwent PET‐CT within 60 days of a new diagnosis (before therapy commenced) to identify the nature and prognostic impact of PET‐CT abnormalities. Patients (N = 313) were seen from April 2005 through June 2017. Of the 234 patients (75%) with focal lesions (FLs), 182 (58%) had at least 3 FLs, 38 (12%) had EMD, and 204 (65%) had documented myelomatous lytic lesions. The median maximum standardized uptake value (SUVmax) for the entire cohort was 5.9 (range 1.5‐48.3). Presence of at least 3 FLs and EMD predicted inferior overall survival (OS); median OS was 57.8 months for patients with 3 or more FLs and 103.6 months for patients with fewer than 3 FLs (P = .003). The median OS was 45.5 and 71.8 months for patients with and without EMD, respectively (P = .004). No clear SUVmax cutoff was predictive of progression‐free survival or OS. PET‐CT is a valuable tool for assessing disease burden and could provide prognostic information about a contemporary cohort of patients with newly diagnosed myeloma who received treatment with novel agents.

SummaryBackgroundIrritable bowel syndrome (IBS) is multifactorial in nature, and a wide range of therapies is available to manage symptoms of this common disorder.AimTo provide an overview of the safety of interventions that may be used to manage patients with diarrhoea‐predominant IBS (IBS‐D).MethodsMedline and Embase database searches (through 02 May 2018) to identify clinical studies that evaluated treatment safety and/or efficacy in adults with IBS‐D.ResultsIBS‐D treatments include dietary modification, probiotics, serotonin receptor antagonists, opioid receptor agonists and antagonists, nonsystemic antibiotics, bile acid sequestrants, antidepressants, and complementary and alternative therapies. These treatments vary in administration frequency (eg, daily; short‐course therapy) and target various pathophysiologic factors. Safety profiles vary considerably by treatment among IBS‐D therapies. The number needed to harm (defined as the number of patients treated to encounter an adverse event) was lowest (worse) for antidepressants (8.5) and highest (best) for probiotics (35), and the number needed to harm (defined as the number of patients who discontinued due to an adverse event) was lowest for tricyclic antidepressants (9) and highest for rifaximin (8971). Notable safety concerns with IBS‐D treatments include pancreatitis with eluxadoline, ischaemic colitis and serious complications of constipation with alosetron, and cardiac adverse events with loperamide and tricyclic antidepressants. Treatment decisions need to account for medication risks and adverse events for each patient.ConclusionsMultiple treatment options are now available for patients with IBS‐D. However, the safety profiles of these agents vary widely by number needed to harm value. Providers should consider both safety and efficacy of a specific intervention when determining how best to manage patients’ IBS‐D symptoms.