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Old Greenwich, CT, United States

Lipstein M.,University of Rochester | O'Connor O.,New York University | Montanari F.,New York University | Paoluzzi L.,Greenwich Hospital | And 2 more authors.
Clinical Lymphoma, Myeloma and Leukemia | Year: 2010

Plasmablastic lymphoma (PBL) is an aggressive lymphoma classified by the World Health Organization as a subtype of diffuse large B-cell lymphoma that shares many morphologic and immunophenotypic features with multiple myeloma. It is extremely rare in immunocompetent patients. Because of the small number of patients reported, this rare lymphoma remains a poorly characterized and understood entity with presently no standard recommendations regarding the optimal treatment. Herein, we report a dramatic clinical response coupled with tumor lysis syndrome to a bortezomib-based treatment in an HIV-negative patient with refractory plasmablastic lymphoma.

DeLong A.K.,Brown University | Blossom B.,Colorado State University | Maloney E.L.,Partnership for Healing and Health Ltd | Phillips S.E.,Greenwich Hospital
Contemporary Clinical Trials | Year: 2012

Introduction: Lyme disease (Lyme borreliosis) is caused by the tick-borne spirochete Borrelia burgdorferi. Long-term persistent illness following antibiotic treatment is not uncommon, particularly when treatment is delayed. Current treatment guidelines for persistent disease primarily rely on findings from four randomized, controlled trials (RCTs), strongly advising against retreatment. Methods: We performed a biostatistical review of all published RCTs evaluating antibiotic retreatment, focusing on trial design, analysis and conclusions. Results: Four RCTs met the inclusion criteria; all examined the efficacy of intravenous ceftriaxone versus placebo at approximately 3 or 6. months. Design assumptions for the primary outcomes in the two Klempner trials and two outcomes in the Krupp trial were unrealistic and the trials were likely underpowered to detect clinically meaningful treatment effects. The Klempner trials were analyzed using inefficient statistical methods. The Krupp RCT was well-designed and analyzed for fatigue, finding statistically significant and clinically meaningful improvement. Fallon corroborated this finding. Fallon also found improvement in cognitive functioning, a primary outcome, at 12. weeks which was not sustained at 24. weeks; improvements in physical functioning and pain were demonstrated at week 24 as an interaction effect between treatment and baseline symptom severity with the drug effect increasing with higher baseline impairment. Discussion: This biostatistical review reveals that retreatment can be beneficial. Primary outcomes originally reported as statistically insignificant were likely underpowered. The positive treatment effects of ceftriaxone are encouraging and consistent with continued infection, a hypothesis deserving additional study. Additional studies of persistent infection and antibiotic treatment are warranted. © 2012 Elsevier Inc.

Brennan C.,Sloan Kettering Cancer Center | Yang T.J.,Sloan Kettering Cancer Center | Hilden P.,Sloan Kettering Cancer Center | Zhang Z.,Sloan Kettering Cancer Center | And 10 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2014

Purpose To evaluate local control after surgical resection and postoperative stereotactic radiosurgery (SRS) for brain metastases. Methods and Materials A total of 49 patients (50 lesions) were enrolled and available for analysis. Eligibility criteria included histologically confirmed malignancy with 1 or 2 intraparenchymal brain metastases, age ≥18 years, and Karnofsky performance status (KPS) ≥70. A Cox proportional hazard regression model was used to test for significant associations between clinical factors and overall survival (OS). Competing risks regression models, as well as cumulative incidence functions, were fit using the method of Fine and Gray to assess the association between clinical factors and both local failure (LF; recurrence within surgical cavity or SRS target), and regional failure (RF; intracranial metastasis outside of treated volume). Results The median follow-up was 12.0 months (range, 1.0-94.1 months). After surgical resection, 39 patients with 40 lesions were treated a median of 31 days (range, 7-56 days) later with SRS to the surgical bed to a median dose of 1800 cGy (range, 1500-2200 cGy). Of the 50 lesions, 15 (30%) demonstrated LF after surgery. The cumulative LF and RF rates were 22% and 44% at 12 months. Patients who went on to receive SRS had a significantly lower incidence of LF (P=.008). Other factors associated with improved local control include non-small cell lung cancer histology (P=.048), tumor diameter <3 cm (P=.010), and deep parenchymal tumors (P=.036). Large tumors (≥3 cm) with superficial dural/pial involvement showed the highest risk for LF (53.3% at 12 months). Large superficial lesions treated with SRS had a 54.5% LF. Infratentorial lesions were associated with a higher risk of developing RF compared to supratentorial lesions (P<.001). Conclusions Postoperative SRS is associated with high rates of local control, especially for deep brain metastases <3 cm. Tumors ≥3 cm with superficial dural/pial involvement demonstrate the highest risk of LF. © 2014 Elsevier Inc. All rights reserved.

Agbor-Etang B.B.,Greenwich Hospital | Setaro J.F.,Yale University
Current Cardiology Reports | Year: 2015

Ischemic heart disease (IHD) affects about 16 million adults in the USA. Many more individuals likely harbor subclinical coronary disease. Hypertension (HTN) continues to be a potent and widespread risk factor for IHD. Among other Framingham risk factors of tobacco use, diabetes mellitus, dyslipidemia, and left ventricular hypertrophy, HTN plays an independent role in augmenting IHD risk, as well as a multiplicative role with respect to adverse outcomes when HTN is present concurrently with the other major IHD risk factors listed above. Over the past two decades, numerous studies and guideline reports have been presented with the aims of (a) elucidating the pathophysiology of IHD, (b) delineating an ideal blood pressure (BP) threshold at which to institute pharmacotherapy, and (c) defining the optimal pharmacologic elements of a therapeutic regimen. While there are active debates surrounding the existence and relevance of the J curve in IHD patients who have HTN, as well as the numerical level of the BP cutoff justifying drug therapy in the general population, there is a general consensus that the BP target in IHD patients should be lower than 140/90 mmHg. The most appropriate class (or classes) of medication recommended will depend on the comorbid conditions associated with each individual patient. Overall, however, there is no major evidence underscoring a significant difference between drug classes, provided the target BP is achieved, although it should be pointed out that the most recent (2015) American Heart Association (AHA)/American College of Cardiology (ACC)/American Society of Hypertension (ASH) guideline statement now elevates beta-blockers (BB) to the same level of recommendation as other classes of hypertension drugs in the treatment of patients who have hypertension and ischemic heart disease. Although most agents that reduce blood pressure will correspondingly lower myocardial workload, BB may exhibit a special advantage in IHD patients because BB (as well as verapamil and diltiazem subclasses of calcium channel blockers or CCB) act to lower HR as well as cardiac inotropy. Moreover, BB will remain an integral if not indispensable part of the management of IHD, especially in those with history of angina pectoris or MI, based on decades of favorable clinical as well as trial experience. This extensive salutary historical background has served as a foundation for the 2015 committee’s decision to bring BB into the front rank of BP agents for those hypertensive individuals suffering simultaneously from IHD. © 2015, Springer Science+Business Media New York.

Finnerup N.B.,University of Aarhus | Attal N.,French Institute of Health and Medical Research | Attal N.,University of Versailles | Haroutounian S.,University of Washington | And 22 more authors.
The Lancet Neurology | Year: 2015

Background: New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods: Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January, 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fixed-effects Mantel-Haenszel method. Findings: 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-reviewed journals reported greater effects than did unpublished studies (r2 9·3%, p=0·009). Trial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2-8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5-9·4) for pregabalin; 7·2 (5·9-9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4-19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, final quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These findings permitted a strong recommendation for use and proposal as first-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation: Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest efficacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profiling probably account for moderate trial outcomes and should be taken into account in future studies. Funding: NeuPSIG of the International Association for the Study of Pain. © 2015 Elsevier Ltd.

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