Felicia L Trachtenberg

New England Research Institutes, Watertown, Massachusetts, United States

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Publications (102)455.57 Total impact

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    Blood; 07/2015
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    ABSTRACT: Pulmonary hypertension (PH) commonly develops in thalassaemia syndromes, but is poorly characterized. The goal of this study was to provide a comprehensive description of the cardiopulmonary and biological profile of patients with thalassaemia at risk for PH. A case-control study of thalassaemia patients at high versus low PH-risk was performed. A single cross-sectional measurement for variables reflecting cardiopulmonary status and biological pathophysiology were obtained, including Doppler-echocardiography, 6-min-walk-test, Borg Dyspnoea Score, New York Heart Association functional class, cardiac magnetic resonance imaging (MRI), chest-computerized tomography, pulmonary function testing and laboratory analyses targeting mechanisms of coagulation, inflammation, haemolysis, adhesion and the arginine-nitric oxide pathway. Twenty-seven thalassaemia patients were evaluated, 14 with an elevated tricuspid-regurgitant-jet-velocity (TRV) ≥ 2·5 m/s. Patients with increased TRV had a higher frequency of splenectomy, and significantly larger right atrial size, left atrial volume and left septal-wall thickness on echocardiography and/or MRI, with elevated biomarkers of abnormal coagulation, lactate dehydrogenase (LDH) levels and arginase concentration, and lower arginine-bioavailability compared to low-risk patients. Arginase concentration correlated significantly to several echocardiography/MRI parameters of cardiovascular function in addition to global-arginine-bioavailability and biomarkers of haemolytic rate, including LDH, haemoglobin and bilirubin. Thalassaemia patients with a TRV ≥ 2·5 m/s have additional echocardiography and cardiac-MRI parameters suggestive of right and left-sided cardiac dysfunction. In addition, low arginine bioavailability may contribute to cardiopulmonary dysfunction in β-thalassaemia. © 2015 John Wiley & Sons Ltd.
    British Journal of Haematology 04/2015; 169(6). DOI:10.1111/bjh.13452 · 4.96 Impact Factor
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    ABSTRACT: Sudden unexplained death in infants, including the sudden infant death syndrome, is likely due to heterogeneous causes that involve different intrinsic vulnerabilities and/or environmental factors. Neuropathologic research focuses upon the role of brain regions, particularly the brainstem, that regulate or modulate autonomic and respiratory control during sleep or transitions to waking. The hippocampus is a key component of the forebrain–limbic network that modulates autonomic/respiratory control via brainstem connections, but its role in sudden infant death has received little attention. We tested the hypothesis that a well-established marker of hippocampal pathology in temporal lobe epilepsy—focal granule cell bilamination in the dentate, a variant of granule cell dispersion—is associated with sudden unexplained death in infants. In a blinded study of hippocampal morphology in 153 infants with sudden and unexpected death autopsied in the San Diego County medical examiner’s office, deaths were classified as unexplained or explained based upon autopsy and scene investigation. Focal granule cell bilamination was present in 41.2 % (47/114) of the unexplained group compared to 7.7 % (3/39) of the explained (control) group (p < 0.001). It was associated with a cluster of other dentate developmental abnormalities that reflect defective neuronal proliferation, migration, and/or survival. Dentate lesions in a large subset of infants with sudden unexplained death may represent a developmental vulnerability that leads to autonomic/respiratory instability or autonomic seizures, and sleep-related death when the infants are challenged with homeostatic stressors. Importantly, these lesions can be recognized in microscopic sections prepared in current forensic practice. Future research is needed to determine the relationship between hippocampal and previously reported brainstem pathology in sudden infant death. Electronic supplementary material The online version of this article (doi:10.1007/s00401-014-1357-0) contains supplementary material, which is available to authorized users.
    Acta Neuropathologica 11/2014; 129. DOI:10.1007/s00401-014-1357-0 · 9.78 Impact Factor
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    British Journal of Haematology 05/2014; 166(5). DOI:10.1111/bjh.12903 · 4.96 Impact Factor
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    ABSTRACT: Because of internet searches, advice from friends, and pharmaceutical advertising, especially direct-to-consumer advertising, patients are increasingly activated to request medications during a physician encounter.
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    ABSTRACT: Thalassemia, a chronic blood disease, necessitates life-long adherence to blood transfusions and chelation therapy to reduce iron overload. We examine stability of health-related quality of life (HRQOL) in thalassemia and adherence to chelation therapy over time, especially after changes in chelator choice. Thalassemia Longitudinal Cohort participants in the USA, UK, and Canada completed the SF-36v2 (ages 14+) and the PF-28 CHQ (parents of children <14 years). Chelation adherence was defined as self-reported percent of doses administered in the last 4 weeks. Two hundred and fifty-eight adults/adolescents (mean 29.7 years) and 133 children (mean 8.5 years) completed a mean of 2.8-years follow-up. Children made few chelator changes, whereas a mean of 2.2 changes was observed among the 37 % of adults/adolescents who made chelator changes, mainly due to patient preference or medical necessity. Physical HRQOL improved among those with lower iron burden (better health status) at baseline who made a single change in chelator, but declined among participants with multiple changes and/or high iron burden (worse health status). Mental health improved among participants with lower iron burden, but iron overload was negatively associated with social functioning. Adherence did not significantly change over follow-up except for an increase after a change from deferoxamine (DFO) infusion to oral deferasirox (p = 0.03). Predictors of lower adherence for adults/adolescents at follow-up included side effects, smoking, younger age, problems preparing DFO, increased number of days per week DFO prescribed, and lower physical quality of life . Strategies to balance medical needs with family, work, and personal life may assist in adherence.
    Quality of Life Research 03/2014; 23(8). DOI:10.1007/s11136-014-0671-2 · 2.86 Impact Factor
  • F L Trachtenberg, P Shrader, L Barregard, N N Maserejian
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    ABSTRACT: Objective To examine whether greater exposure to resin-based composite materials, which may intra-orally release bisphenol A (BPA), is associated with worse renal function outcomes in children.Design Prospective multi-centre study.Setting Community health dental clinics in Boston and Maine from 1997-2005.Subjects and methods Five hundred and thirty-four New England Children's Amalgam Trial participants aged six to ten years were randomised to treatment with amalgam or resin-based composite restorations over five years of follow-up.Interventions Restorations were placed according to treatment arm, and sealants placed per standard of care. Cumulative composite exposure was calculated using surface-years (each treated surface weighted by number years present).Main outcome measures Urinary excretion of albumin, gamma-glutamyl transpeptidase (gamma-GT), and N-acetyl-β-D-glucosaminidase (NAG) were available for 417 children.Results Analysis of covariance showed no association between exposure to dental composites, polyacid-modified compomer, or flowable composite dental sealants and preventative resin restorations with levels of renal function. There was no association between composite materials and thresholds indicating renal damage in logistic regression models.Conclusions This study found no harmful associations between dental composite materials and renal function in children. Therefore, concerns about renal function need not be a consideration in the choice of dental restoration material or placement of preventative dental sealants.
    British dental journal official journal of the British Dental Association: BDJ online 01/2014; 216(2):E4. DOI:10.1038/sj.bdj.2014.36 · 1.08 Impact Factor
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    ABSTRACT: To examine whether medical decisions regarding evaluation and management of musculoskeletal pain conditions varied systematically by characteristics of the patient or provider. We conducted a balanced factorial experiment among primary care physicians in the US. Physicians (n = 192) viewed 2 videos of different patients (actors) presenting with pain: undiagnosed sciatica symptoms or diagnosed knee osteoarthritis. Systematic variations in patient gender, socioeconomic status, and race and physician gender and experience (<20 versus ≥20 years in practice) permitted estimation of unconfounded effects. Analysis of variance was used to evaluate associations between patient or provider attributes and clinical decisions. Quality of decisions was defined based on the current recommendations of the American College of Rheumatology, American Pain Society, and clinical expert consensus. Despite current recommendations, less than one-third of physicians would provide exercise advice (30.2% for osteoarthritis and 32.8% for sciatica). Physicians with fewer years in practice were more likely to provide advice on lifestyle changes, particularly exercise (P ≤ 0.01), and to prescribe nonsteroidal antiinflammatory drugs for pain relief, both of which were appropriate and consistent with current recommendations for care. Newer physicians ordered fewer tests, particularly basic laboratory investigations or urinalysis. Test ordering decreased as organizational emphasis on business or profits increased. Patient factors and physician gender had no consistent effects on pain evaluation or treatment. Physician education on disease management recommendations regarding exercise and analgesics and implementation of quality measures may be useful, particularly for physicians with more years in practice.
    01/2014; 66(1):147-56. DOI:10.1002/acr.22143
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    ABSTRACT: Dental sealant materials may intraorally release their components, including bisphenol-A (BPA), but long-term health effects are uncertain. The New England Children's Amalgam Trial (NECAT) found that composite restorations were associated with psychosocial, but not neuropsychological or physical, outcomes. The previous analysis did not consider sealants and preventive resin restorations (PRRs), which were routinely placed. The purpose of this analysis was to examine sealant/PRR exposure in association with psychosocial and other health outcomes. NECAT recruited 534 six- to 10-year-olds and provided dental care during a five-year follow-up. Annually, examiners conducted psychosocial and neuropsychological tests and measured body mass index (BMI) and fat percentage (BF%). Associations between surface years (SY) of sealants/PRRs and outcomes were tested using multivariable models. Cumulative exposure level to sealants and/or PRRs was not associated with psychosocial assessments (eg, total problems: Child Behavior Checklist, 10-SY β=-0.2±0.3, P=.60) or neuropsychological tests (eg, full-scale IQ, 10-SY β=0.1±0.2, P=.60). There were no associations for changes in BMI-for-age z-score (P=.40), BF% (girls 10-SY β=-0.2±0.3; boys 10-SY β=-0.1±0.3), or menarche (10-SY hazard ratio=0.91, 95% confidence interval=0.83-1.01, P=.08). This study showed no associations between exposure level of dental sealants or PRRs and behavioral, neuropsychological, or physical development in children over 5-years.
    01/2014; 36(1):68-75.
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    ABSTRACT: OBJECTIVE:Sudden and unexplained death is a leading cause of infant mortality. Certain characteristics of the sleep environment increase the risk for sleep-related sudden and unexplained infant death. These characteristics have the potential to generate asphyxial conditions. We tested the hypothesis that infants may be exposed to differing degrees of asphyxia in sleep environments, such that vulnerable infants with a severe underlying brainstem deficiency in serotonergic, γ-aminobutyric acid-ergic, or 14-3-3 transduction proteins succumb even without asphyxial triggers (eg, supine), whereas infants with intermediate or borderline brainstem deficiencies require asphyxial stressors to precipitate death.METHODS:We classified cases of sudden infant death into categories relative to a "potential asphyxia" schema in a cohort autopsied at the San Diego County Medical Examiner's Office. Controls were infants who died with known causes of death established at autopsy. Analysis of covariance tested for differences between groups.RESULTS:Medullary neurochemical abnormalities were present in both infants dying suddenly in circumstances consistent with asphyxia and infants dying suddenly without obvious asphyxia-generating circumstances. There were no differences in the mean neurochemical measures between these 2 groups, although mean measures were both significantly lower (P < .05) than those of controls dying of known causes.CONCLUSIONS:We found no direct relationship between the presence of potentially asphyxia conditions in the sleep environment and brainstem abnormalities in infants dying suddenly and unexpectedly. Brainstem abnormalities were associated with both asphyxia-generating and non-asphyxia generating conditions. Heeding safe sleep messages is essential for all infants, especially given our current inability to detect underlying vulnerabilities.
    PEDIATRICS 11/2013; 132(6). DOI:10.1542/peds.2013-0700 · 5.30 Impact Factor
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    ABSTRACT: Because of exposure to pharmaceutical advertising in different media outlets, especially direct to consumer advertising (DTCA), patients are increasingly activated to request a specific medication during an encounter with a physician. To estimate the effect of patient requests for specific medications on physician prescribing behavior, unconfounded by selected patient attributes (age, race/ethnicity, SES), physician characteristics (gender, experience) and many practice setting factors. Employing balanced factorial experimental methods two clinically authentic video-based scenarios were presented: an undiagnosed patient with symptoms strongly suggesting sciatica, and a patient with already diagnosed chronic osteoarthritis of the knee. Half of the patients with sciatic symptoms specifically requested oxycodone, while the other half simply requested something to help with pain. Similarly, half of those with knee osteoarthritis specifically requested Celebrex. Community-based primary care physicians from several different US states were recruited as experimental subjects (n=192). The primary outcome was whether physicians would accede to a patient request for a specific medication. Alternative pain medications that would be prescribed were secondary outcomes. 19.8% of the sciatic patients specifically requesting oxycodone would receive a prescription, compared with just 1% of those making no request (p=0.001). 53% of patients with knee osteoarthritis requesting celebrex would receive it, compared with 24% of patients making no specific request (p=0.001). Assertive patients requesting oxycodone were more likely to receive a strong narcotic (p=0.001) and less likely to receive a weak narcotic (p=0.01), or an NSAID. Assertive patients requesting celebrex were much less likely to receive a narcotic (p=0.008), or an NSAID. None of the patient attributes, the physician characteristics or the organizational factors influenced a physician's willingness to accede to a patient request for a specific medication. Patients making a request for a specific medication are highly likely to have it prescribed, with the high likelihood of receiving the requested medication consistent across the two scenarios. Who the patient and physician are, and features of the practice setting in which the encounter occurs, have no effect on the success of a medication request. This study suggests that the impact of activated patients on physician decisions potentially increases the total number of patients who become activated and make specific requests of their physicians. Our findings indicate that these requests are often likely to succeed. Since DTCA is used exclusively for expensive medications, generally those like celecoxib that are still available only in branded forms, this effect is likely to increase medication costs.
    141st APHA Annual Meeting and Exposition 2013; 11/2013
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    ABSTRACT: Pain management decisions have been shown to vary by sociodemographic characteristics of patients and providers, and differences exist in the prevalence of diagnosed pain conditions by patient race/ethnicity, sex, age, and socioeconomic status (SES). We conducted a randomized factorial experiment to disentangle characteristics such as patient SES and race while testing the hypothesis that specific patient, physician, or practice organizational factors influence clinical decision-making for pain conditions. From 2010-2012, 192 primary care physicians from six U.S. states were purposefully enrolled to fill design cells of gender and experience. Physician subjects viewed two clinically-authentic videos of patients (actors) presenting with pain either as undiagnosed sciatica symptoms or diagnosed knee osteoarthritis. Patient gender, SES, and race (white, black, Hispanic), and physician gender and experience (<10 vs. >=10 years in practice) systematically varied, permitting estimation of unconfounded effects. Analysis of variance was used for outcomes of physician decision-making, including diagnosis of sciatica and pain management (test ordering, behavioral counseling, prescriptions, referrals). Results showed that 93.7% of physicians appropriately diagnosed sciatica, but there was considerable variation in pain treatment decisions largely unexplained by patient race, gender or provider gender. The treatment of lower vs. higher SES patients with sciatica symptoms were generally similar, e.g., x-ray (55% vs. 49%, P=0.4), MRI (32% vs. 35%, P=0.7), exercise counseling (33% vs. 32%, P=0.9), and referrals (20 vs. 23%, P=0.6). However, lower SES patients less frequently received narcotics for sciatica (52.1% vs. SES 68.7%, P=0.01). Patient race had no impact on management of the sciatica patient, yet for the osteoarthritis patient, whites were more likely to receive narcotics (47%, vs. blacks 27%, Hispanics 33%; P=0.03; no significant interaction with SES). Gender had no effects. Physicians in practice <10 y (vs. >10 y) ordered fewer tests, particularly basic lab work or urinalysis, were more likely to prescribe NSAIDs for pain relief, and to provide advice on lifestyle, particularly exercise (P<=.01). MRI for osteoarthritis pain was more commonly used by physicians who reported not using clinical practice guidelines (21% vs. 13%, P=0.04). Overall test ordering decreased as organizational emphasis on business or profits increased. The finding that physicians' length of time in practice, as well as organization emphasis on business, influences pain management decisions indicates a need for the systematic implementation of quality measures. Policy-makers should also develop methods to assure that narcotic analgesics, when appropriate, are prescribed and monitored for patients of various races and socioeconomic levels.
    141st APHA Annual Meeting and Exposition 2013; 11/2013
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    ABSTRACT: Pain reports have become increasingly common and problematic in thalassemia. As patients are living longer, there is a growing need to study pain and to explore its impact on patient lives. The Brief Pain Inventory (BPI) was used quarterly to assess pain and pain interference in patients with thalassemia in North America. The Medical Outcomes Study 36-Item Short Form Health Survey and the Hospital Anxiety and Depression Scale were used to assess quality of life, anxiety and depression. Of the 252 participants, 56% reported pain at least once over the course of this study, with 32% reporting severe pain (7/10); 16% reported pain at all four visits. Increased pain severity significantly interfered with daily life (P<0.001; regression analysis) and participants with more sites of pain showed an increase in the amount of daily activities affected by pain (P=0.001). Participants reporting more visits with pain reported a significantly higher impact on affective and physical function (P<0.001). Physical quality of life decreased with increasing numbers of visits with pain (P<0.001). Those who reported one or more sites of pain showed increased symptoms of both depression (P<0.001) and anxiety (P=0.003). Participants reporting at least two visits with pain had higher symptoms of anxiety (P=0.002) and those with at least three visits reported higher symptoms of depression (P=0.003). Pain is prevalent in thalassemia and is often a chronic condition that interferes with life. The study highlights the significance of pain in thalassemia and its impact, which should be considered in future research and treatments. Am. J. Heamtol. 88:939-943, 2013. (c) 2013 Wiley Periodicals, Inc.
    American Journal of Hematology 11/2013; 88(11):939-943. DOI:10.1002/ajh.23565 · 3.48 Impact Factor
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    ABSTRACT: Resins used in dental composites, derived from bisphenol-A (BPA), have been shown to alter immune cells. The objective of this study was to explore children's immune function changes in relation to resin composite treatment. We conducted secondary data analysis of the New England Children's Amalgam Trial immune function substudy (N = 59). Immune function was measured pre-treatment and up to five times post-treatment through 5-year follow-up. Multivariable generalized linear regression models were used to estimate the association between three classes of resin composites (bisphenol-A-diglycidyl-dimethacrylate [BisGMA]-based flowables used for preventive sealants; urethane dimethacrylate [UDMA]-based compomer restorations; bisGMA-based restorations) and changes in immune function markers measured annually. Total white blood cell counts and responsiveness of T cells or neutrophils were not appreciably altered by composite treatment levels. Changes in B cell responsiveness were greater throughout follow-up among children with more bisGMA-based composite restorations, which opposed findings for amalgam treatment levels. Monocyte responsiveness changes were decreased at 6 months with greater treatment, but not over longer follow-up. Results of this analysis showed no overt immune function alterations associated with resin composites. Additional research regarding lymphocyte activation may be warranted given the consistency of results within these analyses and with a prior study showing increased B cell activation.
    International Journal of Paediatric Dentistry 09/2013; 24(3). DOI:10.1111/ipd.12064 · 1.54 Impact Factor
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    ABSTRACT: Improved survival in thalassemia has refocused attention on quality of life, including family planning. Understanding the issues associated with infertility and adverse pregnancy outcomes may impact clinical care of patients with thalassemia. We report the number and outcomes of pregnancies among subjects enrolled in Thalassemia Clinical Research Network (TCRN) registries and examine variables associated with successful childbirth. We identified 129 pregnancies in 72 women among the 264 women, age 18 years or older in our dataset. Over 70% of pregnancies resulted in live births and 73/83 (88%) of live births occurred at full term. Most pregnancies (78.2%) were conceived without reproductive technologies. Most (59.3%) pregnancies occurred while on chronic transfusion programs, however only 38.9% were on iron chelation. Four women developed heart problems. Iron burden in women who had conceived was not significantly different from age- and diagnosis-matched controls that had never been pregnant. There was also no difference in pregnancy outcomes associated with diagnosis, transfusion status, diabetes or Hepatitis C infection. Pregnancies occurred in 27.3% of women with thalassemia of child-bearing age in the TCRN registries, a notable increase from our previous 2004 report. With optimal health maintenance, successful pregnancies may be achievable.
    American Journal of Hematology 09/2013; 88(9):771-773. DOI:10.1002/ajh.23506 · 3.48 Impact Factor
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    ABSTRACT: Background Established heart failure in thalassaemia major has a poor prognosis and optimal management remains unclear. Methods A 1 year prospective study comparing deferoxamine (DFO) monotherapy or when combined with deferiprone (DFP) for patients with left ventricular ejection fraction (LVEF) <56% was conducted by the Thalassemia Clinical Research Network (TCRN). All patients received DFO at 50–60 mg/kg 12–24 hr/day sc or iv 7 times weekly, combined with either DFP 75 at mg/kg/day (combination arm) or placebo (DFO monotherapy arm). The primary endpoint was the change in LVEF by CMR. Results Improvement in LVEF was significant in both study arms at 6 and 12 months (p = 0.04), normalizing ventricular function in 9/16 evaluable patients. With combination therapy, the LVEF increased from 49.9% to 55.2% (+5.3% p = 0.04; n = 10) at 6 months and to 58.3% at 12 months (+8.4% p = 0.04; n = 7). With DFO monotherapy, the LVEF increased from 52.8% to 55.7% (+2.9% p = 0.04; n = 6) at 6 months and to 56.9% at 12 months (+4.1% p = 0.04; n = 4). The LVEF trend did not reach statistical difference between study arms (p = 0.89). In 2 patients on DFO monotherapy during the study and in 1 patient on combined therapy during follow up, heart failure deteriorated fatally. The study was originally powered for 86 participants to determine a 5% difference in LVEF improvement between treatments. The study was prematurely terminated due to slow recruitment and with the achieved sample size of 20 patients there was 80% power to detect an 8.6% difference in EF, which was not demonstrated. Myocardial T2* improved in both arms (combination +1.9 ± 1.6 ms p = 0.04; and DFO monotherapy +1.9 ± 1.4 ms p = 0.04), but with no significant difference between treatments (p = 0.65). Liver iron (p = 0.03) and ferritin (p < 0.001) both decreased significantly in only the combination group. Conclusions Both treatments significantly improved LVEF and myocardial T2*. Although this is the largest and only randomized study in patients with LV decompensation, further prospective evaluation is needed to identify optimal chelation management in these high-risk patients.
    Journal of Cardiovascular Magnetic Resonance 05/2013; 15(1):38. DOI:10.1186/1532-429X-15-38 · 5.11 Impact Factor
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    ABSTRACT: Pulmonary hypertension is a common but often overlooked complication associated with thalassemia syndromes. There is limited data on the safety and efficacy of selective pulmonary vasodilators in this at-risk population. We therefore designed a 12-week open-label phase 1/2 pilot-scale proof-of-principle trial of sildenafil therapy in 10 patients with beta-thalassemia and increased risk for pulmonary hypertension based upon an elevated tricuspid regurgitant jet velocity >2.5 m/s on Doppler-echocardiography. Variables measured include Doppler-echocardiography, 6-minute walk distance, Borg Dyspnea Score, New York Heart Association functional class, pulmonary function testing, and laboratory analyses compared at baseline and after 12 weeks of sildenafil. Treatment with sildenafil resulted in a significant decrease in tricuspid regurgitant jet velocity by 13.3% (3.0+/-0.7 vs. 2.6+/-0.5m/s, p=0.04), improved left ventricular end systolic/diastolic volume, and a trend towards a improved New York Heart Association functional class. No significant change in six-minute walk distance was noted. Sildenafil was well tolerated, although minor anticipated adverse events were commonly reported. Total dose amount of sildenafil (mg) taken strongly correlated with % change in nitric oxide metabolite concentration in the plasma (ρ =0.80, p=0.01). A significant increase in plasma and erythrocyte arginine concentration also occurred. Our study suggests that sildenafil is safe and may improve pulmonary hemodynamics in patients at risk for pulmonary hypertension; however efficacy with respect to 6-minute walk distance was not demonstrated. Clinical trials are needed to identify the best treatment strategy for pulmonary hypertension in beta-thalassemia. (clinicaltrials.gov identifier: NCT00872170).
    Haematologica 04/2013; DOI:10.3324/haematol.2012.082065 · 5.87 Impact Factor
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    ABSTRACT: Pulmonary hypertension is a common but often overlooked complication associated with thalassemia syndromes. There is limited data on the safety and efficacy of selective pulmonary vasodilators in this at-risk population. We therefore designed a 12-week open-label phase 1/2 pilot-scale proof-of-principle trial of sildenafil therapy in 10 patients with beta-thalassemia and increased risk for pulmonary hypertension based upon an elevated tricuspid regurgitant jet velocity >2.5 m/s on Doppler-echocardiography. Variables measured include Doppler-echocardiography, 6-minute walk distance, Borg Dyspnea Score, New York Heart Association functional class, pulmonary function testing, and laboratory analyses compared at baseline and after 12 weeks of sildenafil. Treatment with sildenafil resulted in a significant decrease in tricuspid regurgitant jet velocity by 13.3% (3.0+/-0.7 vs. 2.6+/-0.5m/s, p=0.04), improved left ventricular end systolic/diastolic volume, and a trend towards a improved New York Heart Association functional class. No significant change in six-minute walk distance was noted. Sildenafil was well tolerated, although minor anticipated adverse events were commonly reported. Total dose amount of sildenafil (mg) taken strongly correlated with % change in nitric oxide metabolite concentration in the plasma (ρ =0.80, p=0.01). A significant increase in plasma and erythrocyte arginine concentration also occurred. Our study suggests that sildenafil is safe and may improve pulmonary hemodynamics in patients at risk for pulmonary hypertension; however efficacy with respect to 6-minute walk distance was not demonstrated. Clinical trials are needed to identify the best treatment strategy for pulmonary hypertension in beta-thalassemia. (clinicaltrials.gov identifier: NCT00872170).
    Haematologica 04/2013; · 5.87 Impact Factor
  • Osteoarthritis and Cartilage 04/2013; 21:S152. DOI:10.1016/j.joca.2013.02.326 · 4.66 Impact Factor
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    ABSTRACT: Pain is not a symptom generally associated with thalassaemia. However, providers have noted increasing patient reports of pain, creating an impetus for this prospective, observational assessment of pain in thalassaemia patients. The primary study goals were to assess pain prevalence, severity, location, and potential risk factors. This was a multicentre, prospective study of thalassaemia patients receiving care at 12 Thalassaemia Clinical Research Network sites. Pain was assessed using the Brief Pain Inventory. Two hundred and fifty-two thalassaemia patients ranging in age from 12 to 71 years (mean 28·8) were enrolled. Sixty-four per cent reported experiencing pain during the last 4 weeks, 22% of whom reported pain on a daily basis. Ordinal regression analysis of pain ratings demonstrated significant (P < 0·001) correlation of increased age with increased pain, irrespective of diagnosis, transfusion status, gender, bone density, chelator type or iron overload. Eighty-one per cent reported having pain for 1 year or longer and 31% reported pain for five or more years. Pain is a major cause of morbidity and an unrecognized problem for patients with thalassaemia. Age is the strongest predictor of frequency and severity. Little else is known about the aetiology and predictors of this pain syndrome.
    British Journal of Haematology 12/2012; 160(5). DOI:10.1111/bjh.12177 · 4.96 Impact Factor

Publication Stats

3k Citations
455.57 Total Impact Points

Institutions

  • 2004–2014
    • New England Research Institutes
      Watertown, Massachusetts, United States
  • 2011
    • University of Toronto
      Toronto, Ontario, Canada
    • Boston Children's Hospital
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2005–2009
    • Harvard Medical School
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2006
    • Harvard University
      Cambridge, Massachusetts, United States