Citations

ABSTRACT In this study, we compared the performance of six real-time PCR assays for the qualitative detection of cytomegalovirus (CMV) in clinical samples other than plasma. Two hundred specimens (respiratory [ n = 72], urine [ n = 67], cerebrospinal fluid [CSF] [ n = 25], tissue [ n = 18], amniotic fluid [ n = 10], and bone marrow [ n = 8]) submitted for routine testing by CMV real-time PCR analyte-specific reagents (ASR) (Roche Diagnostics, Indianapolis, IN) were also tested by a laboratory-developed test (LDT) and 4 commercially available PCR assays: EraGen Multicode (Luminex, Austin, TX), Focus Simplexa (Focus Diagnostics, Cypress, CA), Elitech MGB Alert CMV (Fisher Scientific, Hanover Park, IL), and Abbott CMV (Abbott Park, IL). Nucleic acid was extracted using the MagNA Pure system (Roche Diagnostics) and subsequently tested by each PCR method. Results were analyzed by comparing each assay to a “consensus result,” which was defined as the result obtained from at least 4 of the 6 assays. In addition to the prospective samples, 13 lower respiratory samples with known positive results by CMV shell vial were tested by each PCR method. Following testing of the 200 prospective specimens, the Abbott, Elitech, EraGen, and Focus PCR assays demonstrated a sensitivity of 100% (46/46), while the Roche analyte-specific reagents (ASR) and LDT showed sensitivities of 89% (41/46) and 98% (45/46), respectively. Percent specificities ranged from 97% (149/154) by Elitech to 100% (154/154) by the LDT. Among the 13 shell vial-positive lower respiratory samples, the percent sensitivities ranged from 69% (9/13) by Elitech to 92% (12/13) by the LDT. The Abbott, EraGen, Elitech, Focus, and LDT PCR assays performed similarly (κ ≥ 0.89) for the detection of CMV in clinical specimens and demonstrated increased sensitivity compared to the Roche ASR.

Objective Bicuspid aortic valve (BAV) is associated with a higher risk of type A aortic dissection (AD) compared with tricuspid aortic valve (TAV). We sought to study differences between patients with BAV and TAV with AD. Design and setting Observational descriptive analysis of clinical, imaging and pathological characteristics of all patients with confirmed BAV and AD from 1980–2010, compared with a consecutive TAV group with AD. Results Of 47 patients with BAV (mean age 58±14, 77% male), 31 (66%) had acute AD, 16 (34%) had chronic AD, 40 (85%) had typical BAV, 32 (68%) had hypertension and 11 (23%) had previous aortic coarctation repair. Of 53 patients with TAV (mean age 66±13 (p=0.007), 76% male), 34 (66%) had acute AD (p=1.0) and 46 (87%) had hypertension (p=0.03). More patients with BAV had known aortic dilatation prior to AD (49% versus 17%, p=0.001). Presentation symptoms were identical between groups (p=NS). Maximal ascending aortic diameter at AD was higher in patients with BAV (66±15 mm vs 56±11 mm, p=0.0004). Previous aortic valve replacement (AVR) was more common in BAV (23% vs 6%, p=0.02). Of 11 patients with BAV with previous isolated AVR, 7 had ≥moderate ascending aorta dilatation at the time of surgery. Patients with BAV had increased aortic jet velocity (28% vs 10%) and more severe aortic stenosis (19% vs 0%) at presentation (p=0.04 and 0.002, respectively). In acute AD, aortic medial degeneration affected 75% of BAV specimens and 41% TAV specimens (p=0.01) while aortic atherosclerosis was more frequent in TAV (56% vs 26%, p=0.02). Conclusions Compared with patients with TAV, patients with BAV with type A AD are younger, have less hypertension, more valve stenosis and previous AVR, higher maximal aortic dimension, worse aortic medial degeneration, high prevalence of aortic coarctation, and 1 out of 2 have known aortic dilatation prior to AD. Implementation of current guidelines could have theoretically prevented AD in several patients with BAV.

BACKGROUNDDrug choice and delivered dose of treatment potentially influence outcome in patients treated for follicular lymphoma (FL). Historically, observational studies have evaluated drug choice. The National LymphoCare Study (NLCS) is a prospective, observational study of patients with FL who were enrolled at academic and community practice sites in the United States between 2004 and 2007. In the current study, the authors report on measures of delivered dose and its impact on outcomes for the most common first‐line regimens.METHODSAll evaluable patients with FL who were treated with initial rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP); rituximab plus cyclophosphamide, vincristine, and prednisone (R‐CVP); or rituximab plus a fludarabine‐containing regimen (R‐Flu) were included. Associations between baseline factors, choice of treatment, number of cycles received, completion of therapy, and patient outcomes were assessed.RESULTSA total of 646 patients received R‐CHOP, 297 received R‐CVP, and 222 received R‐Flu. Characteristics were similar between the 3 groups with the following exceptions. Patients receiving R‐CHOP were more often found to have grade 3 FL and patients receiving R‐CVP were older and had higher Follicular Lymphoma International Prognostic Index scores. The majority of patients (80%) received ≥ 5 cycles of treatment. Toxicity, but not disease progression, was commonly cited as the reason for the early discontinuation of treatment (51% vs 6%). Time to retreatment was shorter for patients receiving ≤ 4 cycles, regardless of the treatment regimen used. The number of cycles was associated with overall survival, progression‐free survival, and lymphoma‐related mortality for patients receiving R‐CVP.CONCLUSIONSThe majority of patients with FL receiving chemoimmunotherapy in the NLCS completed ≥ 5 cycles of treatment. Strategies to improve dose delivery appear unlikely to impact outcomes, except possibly in patients receiving R‐CVP. Although early treatment discontinuation appears to be associated with survival, this analysis does not implicate causality. Cancer 2013;119:4129–4136. © 2013 American Cancer Society.

AbstractGhrelin is the endogenous ligand for the growth hormone secretagogue‐1a receptor and is a potential target for treatment of gastroparesis. This viewpoint assesses the potential role of ghrelin agonists in the treatment of gastroparesis through a review of the early phase, randomized, controlled trials of ghrelin agonists in patients with diabetes and, either, delayed gastric emptying at the time of the trial or symptoms at the time of the trial, and prior documentation of delayed gastric emptying of solids. Whereas recent experience with ghrelin agonists that have a macrocycle structure (TZP‐101, TZP‐102) has not confirmed earlier promising results, there is little evidence that ghrelin receptors downregulate with repeated treatment, in contrast to motilin receptors. Phase IIa clinical trials performed with a different agent (RM‐131, which is a small molecule ghrelin agonist) suggest that, as a class, ghrelin agonists may be efficacious in stimulating gastric emptying. It is premature to dismiss ghrelin agonists as potential therapies for gastroparesis.

AbstractBackgroundLow 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.MethodsPatients 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 ResultsA 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 & InferencesIn 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.

Objective To identify factors associated with triptan discontinuation among migraine patients. Background It is unclear why many migraine patients who are prescribed triptans discontinue this treatment. This study investigated correlates of triptan discontinuation with a focus on potentially modifiable factors to improve compliance. Methods This multicenter cross‐sectional survey (n = 276) was performed at US tertiary care headache clinics. Headache fellows who were members of the American Headache Society Headache Fellows Research Consortium recruited episodic and chronic migraine patients who were current triptan users (use within prior 3 months and for ≥1 year) or past triptan users (no use within 6 months; prior use within 2 years). Univariate analyses were first completed to compare current triptan users to past users for: migraine characteristics, other migraine treatments, triptan education, triptan efficacy, triptan side effects, type of prescribing provider, Migraine Disability Assessment ( MIDAS ) scores and Beck Depression Inventory ( BDI ) scores. Then, a multivariable logistic regression model was selected from all possible combinations of predictor variables to determine the factors that best correlated with triptan discontinuation. Results Compared with those still using triptans (n = 207), those who had discontinued use (n = 69) had higher rates of medication overuse (30 vs 18%, P = .04) and were more likely to have ever used opioids for migraine treatment (57 vs 38%, P = .006) as well as higher MIDAS (mean 63 vs 37, P = .001) and BDI scores (mean 10.4 vs 7.4, P = .009). Compared with discontinued users, current triptan users were more likely to have had their triptan prescribed by a specialist (neurologist, headache specialist, or pain specialist) (74 vs 54%, P = .002) and were more likely to report headache resolution (53 vs 14%, P < .001) or a reduction in pain intensity (71 vs 28%, P < .001) most of the time from their triptan. On a 1‐5 scale (1 = disagree, 5 = agree), triptan users felt they had more: control over their migraine attacks (2.9 vs 2.1), confidence in their prescribing provider (4.5 vs 4.0), and were more educated about triptan use (4.2 vs 3.7) compared with triptan discontinuers ( P < .001 for all comparisons). Although both current and prior users reported similar rates of side effects (48 vs 43%, P = .44), of those who discontinued use, the main reasons were for lack of effect (44%) and side effects (29%). Our multivariable modeling revealed that the strongest correlate of triptan discontinuation was lack of efficacy (odds ratio = 17, 95% confidence interval [8.8, 33.0]). Other factors associated with discontinuation included MIDAS > 24 (2.6, [1.5, 4.6]), BDI >4 (2.5, [1.4, 4.5]), and a history of ever using opioids for migraine therapy (2.2, [1.3, 3.8]). Having a triptan prescribed by a specialist and using at least 1 other abortive medication with the triptan were associated with a decreased likelihood of triptan discontinuation (0.41, [0.2‐0.7] and 0.44 [0.3, 0.8], respectively). Conclusions As expected, discontinuation was most correlated with lack of efficacy, but other important factors associated with those who had discontinued use included greater migraine‐related disability, depression, and the use of opioids for migraine attacks. Compared with patients who had discontinued triptans, current triptan users felt more: educated about their triptan, control over their migraine attacks, and confidence in their prescribing provider. Current triptan users had their triptan prescribed by a specialist and used other abortive medications with their triptan more often compared with patients who had discontinued triptans. Given the cross‐sectional nature of this study, we cannot determine if these factors contributed to triptan discontinuation or reflect the impact of such discontinuation. Interventions that address modifiable risk factors for triptan discontinuation may decrease the likelihood of triptan discontinuation and thus improve overall migraine control. Because lack of efficacy was most strongly associated with triptan discontinuation, future research should determine why triptans are effective for some patients but not others.