Citations

AbstractA well‐designed pilot study can advance science by providing essential preliminary data to support or motivate further research, refine study logistics, and demonstrate proof of concept. Often, the outcomes of such studies can be quantified by a success/failure dichotomy. For example, a novel compound may show activation of a neural pathway, or it may not. When an intervention's efficacy is quantified using a dichotomous outcome, probability mass functions can be enumerated to determine the probability that the observed result from a pilot study supports further evaluation of the intervention since there is only a finite, and often small, number of sample configurations possible. The purpose of this research was to determine the probability of an “efficacy signal” for pilot studies using one‐ and two‐sample pilot study designs. Efficacy signal was defined as the probability of observing a more favorable response proportion relative to a historical control (one‐sample setting) or to a concurrent control (two‐sample setting). An enumeration study (exact simulation) was conducted to calculate the efficacy signal probability. One‐sample study designs yielded higher probability of determining an efficacy signal than the two‐sample setting; however, sampling variation must be accounted for. A 68% score confidence interval is recommended for this purpose.

AbstractUtilizing billing records, we identified patients seen at Mayo Clinic with a diagnosis or history of fibromyalgia who were then contacted for enrollment in a fibromyalgia research registry. Fibromyalgia was confirmed through medical record review. Eligible patients were mailed an invitation that included a demographic questionnaire and the Fibromyalgia Research Survey. The Fibromyalgia Research Survey yields a widespread pain score (scale range 0–19) and a symptom severity score (scale range 0–12). A total of 4,034 patients returned the completed survey; 92.8% were female, their mean age was 57.4 (±13.4), and 83.7% were from the Midwest region of the United States. The mean widespread pain score for all participants was 11.3 (±4.5) and the mean symptom severity score was 8.2 (±2.4), indicating moderate‐to‐severe fibromyalgia symptoms, which is not unusual for patients presenting to a tertiary care center. Using a systematic process, we describe the creation of a fibromyalgia registry for future research.

Background and Purpose— Acute intraprocedural thrombus formation complicating endovascular cerebral aneurysm treatment is often treated with intra-arterial or intravenous administration of thrombolytic agents or glycoprotein IIb/IIIa (GpIIb/IIIa) inhibitors. We sought to evaluate the morbidity and mortality associated with such treatments using a large multihospital database. Methods— Using the Premier Perspective Database, we examined outcomes for patients receiving endovascular coiling for ruptured and unruptured aneurysms requiring rescue therapy, defined as treatment with GpIIb/IIIa inhibitors and fibrinolytic therapy. We compared discharge status, length of stay, and complication rates across 3 groups: (1) patients receiving GpIIb/IIIa inhibitors only, (2) patients receiving fibrinolytic therapy only, and (3) patients receiving both GpIIb/IIIa inhibitors and fibrinolytics. Student t test was used to compare continuous variables, and Fisher exact test was used to compare categorical variables. Results— Seven-percent (254/3627) of patients treated for unruptured aneurysms received rescue therapy. When compared with patients receiving GpIIb/IIIa inhibitors alone, patients receiving only fibrinolytics had significantly higher rates of discharge to institutions other than home (37.5% [9/24] versus 7.4% [15/201]; P <0.0001). Eight-percent of patients (338/4204) treated for ruptured aneurysms received rescue therapy. When compared with patients receiving GpIIb/IIIa inhibitors alone, patients receiving only fibrinolytics had significantly higher rates of mortality (26.0% [18/69] versus 14.5% [35/241]; P =0.02) and discharge to institutions other than home (59.4% [41/69] versus 36.5% [88/241]; P <0.0001). Conclusions— Pharmacological rescue therapy occurred in 7% to 8% of endovascular coiling patients with unruptured and ruptured intracranial aneurysms. Rescue therapy with thrombolytic agents resulted in significantly more morbidity and mortality than rescue therapy with GpIIb/IIIa inhibitors.

Disease OverviewImmunoglobulin (Ig) light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of Ig light chain are deposited in tissues. Clinical features depend on organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, peripheral/autonomic neuropathy, and atypical multiple myeloma.DiagnosisTissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients. Verification that amyloid is of immunoglobulin origin is mandatory.PrognosisN‐terminal pro–brain natriuretic peptide (NT‐proBNP), serum troponin T, and immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8 months.TherapyAll patients with a visceral amyloid syndrome require therapy to prevent deposition of amyloid in other viscera and prevent progressive organ failure of involved sites. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include NT‐proBNP <5,000 ng/mL, troponin T < 0.06 ng/mL, age <70 years, <3 organs involved, and serum creatinine ≤1.7 mg/dL. Nontransplant candidates can be offered melphalan‐dexamethasone. Pomalidomide appears to have activity, as do other combinations of chemotherapy with agents such as cyclophosphamide‐thalidomide (or lenalidomide or bortezomib)‐dexamethasone, bortezomib‐dexamethasone, and melphalan‐prednisone‐lenalidomide.Future ChallengesLate diagnosis remains a major obstacle to initiating effective therapy when organ dysfunction is still recoverable. Recognizing the presenting syndromes is necessary for improving survival. Am. J. Hematol. 88:417–425, 2013. © 2013 Wiley Periodicals, Inc.

AbstractBackgroundMicrobial constituents of the gut microbiome interact with each other and the host to alter the luminal environment and impact development, motility, and homeostasis of the gut. Powerful methods are becoming available to investigate connections between the gut microbiome and human health. While high‐throughput sequencing of 16S rRNA genes can be used to identify and enumerate microbes in the gut, advances in several techniques (e.g., metagenomics, metatranscriptomics, metabolomics, and metaproteomics) are providing a clearer view as to the specific activities of the microbiota in the context of functional host–microbe interactions. Testing emergent hypotheses regarding microbial effects on host biology, which arise from analyses of ‘Big Data’ generated from massive parallel high‐throughput sequencing technology and spectroscopic techniques, to guide translational research is an important goal for the future. Insights regarding the fundamental operating principles of the gut microbiota should lay the foundation for rational manipulation of the microbiota to promote human health.PurposeIn this review, we provide an overview of current research on the gut microbiome emphasizing current state‐of‐the‐art technologies, approaches, and directions for improvement of our understanding of the impact of the gut microbiota with specific focus on gastrointestinal motility disorders.

SummaryDexamethasone ± thalidomide with infusion of cisplatin, doxorubicin, cyclophosphamide, and etoposide [D(T)PACE] is generally reserved as salvage therapy for aggressive multiple myeloma (MM) or plasma cell leukaemia (PCL) resistant to conventional therapies. The efficacy and durability of this potentially toxic regimen in this setting is unclear. We identified 75 patients who received D(T)PACE for relapsed/refractory MM at two tertiary care centres: Princess Margaret Hospital, Toronto and Mayo Clinic Arizona. At time of D(T)PACE, 16 patients had PCL and three patients had leptomeningeal disease. Patients were heavily pretreated (median three prior regimens, range 1–12; prior autologous stem cell transplant [ASCT] 33%). Overall response rate was 49% (very‐good partial response 16%, partial response 33%) with stable disease in an additional 36%. Median progression‐free survival (PFS) was 5·5 months (95% confidence interval [CI]:4·3–9·8); overall survival (OS) 14·0 months (95% CI:8·7–19·3). Thirty‐five patients proceeded to ASCT or clinical trial, with median PFS for this subset of 13·4 months (95% CI:7·7–20·1) and OS 20·5 months (95% CI:14·8–63·8). D(T)PACE is an effective salvage therapy for heavily pretreated MM patients. Although the overall response rate of 49% in this poor prognosis cohort is reasonable, the PFS is short, suggesting the best role for D(T)PACE is in bridging to definitive therapy, such as transplantation.

Key Points Low-count and high-count monoclonal B-cell lymphocytosis (MBL) have distinct immunogenetic signatures, with only the latter resembling CLL. Rather than a true premalignant condition, low-count MBL may merely reflect immune senescence or result from persistent antigen stimulation.