Felicia L Trachtenberg

New England Research Institutes, 워터타운, Massachusetts, United States

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Publications (125)502.26 Total impact

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    ABSTRACT: Purpose: Sudden unexplained death in childhood (SUDC), while rare, accounts for an important fraction of unexpected deaths in children >1 year of age. Previously we reported an association between febrile seizures, hippocampal maldevelopment, and sudden, unexpected deaths in young children (1-6 years), termed "hippocampal maldevelopment associated with sudden death (HMASD)." Here, we characterize in greater detail the hippocampal pathology in a large cohort of cases (n = 42) of this entity, and attempt to define possible new entities responsible for sudden, unexplained death in young children without HMASD/febrile seizure phenotypes. Methods: We performed comparative analysis on cases, which we classified in a cohort of 89 sudden and unexpected deaths as HMASD, explained deaths, SUDC with febrile seizure phenotype (SUDC-FS) but without hippocampal pathology, and SUDC (without hippocampal pathology or febrile seizure phenotype). Results: The frequency of each subgroup was: HMASD 48 % (40/83); SUDC 27 % (22/83); SUDC-FS 18 % (15/83); explained 7 % (6/83). HMASD was characterized clinically by sudden, sleep-related death, term birth, and discovery in the prone position. Key morphologic features of HMASD were focal granule cell bilamination of the dentate gyrus with or without asymmetry and/or malrotation of the hippocampus, associated with significantly increased frequencies of 11 other developmental abnormalities. We identified no other distinct phenotype in the unexplained categories, except for an association of febrile seizures without hippocampal maldevelopment. Conclusions: HMASD is a distinct clinicopathologic entity characterized by a likely developmental failure of neuronal migration in the dentate gyrus. Future research is needed to determine the causal role of HMASD in sudden death in early childhood.
    No preview · Article · Jan 2016 · Forensic Science Medicine and Pathology
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    ABSTRACT: Purpose: The purpose of this study was to determine the major subcategories and clinicopathologic features of sudden unexpected death in young children in a large retrospective cohort, and to confirm the association of sudden unexplained death in children (abbreviated by us for unexplained deaths as SUDC) with hippocampal pathology and/or febrile seizures. Methods: We undertook analysis of a retrospective cohort of 151 cases, of which 80 % (121/151) were subclassified as SUDC, 11 % (16/151) as explained, 7 % (10/151) as undetermined, and 3 % (4/151) as seizure-related. Results: There were no significant differences between SUDC and explained cases in postnatal, gestational, or postconceptional age, frequency of preterm birth, gender, race, or organ weights. In contrast, 96.7 % (117/121) of the SUDC group were discovered during a sleep period compared to 53.3 % (8/15) of the explained group (p < 0.001), and 48.8 % (59/121) of the SUDC cases had a personal and/or family history of febrile seizures compared to 6.7 % (1/15) of the explained group (p < 0.001). Of the explained deaths, 56 % (9/16) were subclassified as infection, 31 % (5/16) cardiac, 6 % (1/16) accidental, and 6 % (1/16) metabolic. Two of the three cases specifically tested for cardiac channelopathies at autopsy based upon clinical indications had genetic variants in cardiac genes, one of uncertain significance. Bacterial cultures at autopsy typically revealed organisms interpreted as contaminants. Two of the four seizure-related deaths were witnessed, with two of the brains from these cases showing generalized malformations. Hippocampal anomalies, including a specific combination we termed hippocampal maldevelopment associated with sudden death, were found in almost 50 % (40/83) of the SUDC and undetermined cases in which hippocampal sections were available. Conclusions: This study highlights the key role for the hippocampus, febrile seizures, and sleep in SUDC pathophysiology. It also demonstrates the role of known predisposing conditions such as cardiac channelopathies and infections in causing sudden unexpected death in childhood, and the need for improved ancillary testing and protective strategies in these cases, even when the cause of death is established at autopsy.
    No preview · Article · Jan 2016 · Forensic Science Medicine and Pathology
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    Richard D Goldstein · Felicia L Trachtenberg · Mary Ann Sens · Brian J Harty · Hannah C Kinney
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    ABSTRACT: Background: Reductions in sudden infant death syndrome (SIDS) are commonly attributed to modifications in infant sleep environments. Approaches to diagnosis in sudden infant death, death scene investigations, the prevalence of intrinsic risk factors for SIDS, and the potential influence of treatment-related factors on infant vulnerability have also changed. Understanding all contributory factors may help reduce residual SIDS rates. Methods: We analyzed US Mortality Multiple Causes Records for 1983 to 2012 to compare SIDS postneonatal mortality rates with a projection applying non-SIDS mortality changes, using those changes as a proxy measure for alterations in intrinsic risk. Composites of neglect-related, unknown, and circumstantial respiratory diagnoses were measured, as was a cumulative composite of unexplained infant death diagnoses. Cluster analysis with leading causes of postneonatal mortality and SIDS mortality rates for low birth weight infants were also examined. Results: SIDS and non-SIDS postneonatal mortality rates were concordant over time. Important variance was seen 1994 to 1996, coinciding with Back-to-Sleep initiation. Other variance, eliminated in the cumulative composite, appeared related to differences in diagnostic practices. Changes in SIDS rates resembled changes in mortality from congenital malformations, respiratory distress of the newborn, and diseases of the circulatory system. SIDS rates for low birth weight infants followed broader postneonatal trends. Conclusions: SIDS mortality followed trends in overall postneonatal mortality, including effects of changes in the infant sleep environment and diagnostic classification. Preventing asphyxia risk in the sleep environment must be coupled with efforts to understand intrinsic biological pathways, some potentially associated with other categories of infant and perinatal mortality.
    Preview · Article · Dec 2015 · Pediatrics

  • No preview · Article · Sep 2015 · Pediatric and Developmental Pathology
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    Full-text · Conference Paper · Jul 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.
    Full-text · Article · Apr 2015 · British Journal of Haematology
  • Felicia L Trachtenberg · David M Pober · Lisa C Welch · John B McKinlay
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    ABSTRACT: Rationale aims and objectives: Variation in physician decisions may reflect personal styles of decision-making, as opposed to singular clinical actions and these styles may be applied differently depending on patient complexity. The objective of this study is to examine clusters of physician decision-making for type 2 diabetes, overall and in the presence of a mental health co-morbidity. Method: This randomized balanced factorial experiment presented video vignettes of a "patient" with diagnosed, but uncontrolled type 2 diabetes. "Patients" were systematically varied by age, sex, race and co-morbidity (depression, schizophrenia with normal or bizarre affect, eczema as control). Two hundred and fifty-six primary care physicians, balanced by gender and experience level, completed a structured interview about clinical management. Results: Cluster analysis identified 3 styles of diabetes management. "Minimalists" (n=84) performed fewer exams or tests compared to "middle of the road" physicians (n=84). "Interventionists" (n=88) suggested more medications and referrals. A second cluster analysis, without control for co-morbidities, identified an additional cluster of "information seekers" (n=15) who requested more additional information and referrals. Physicians ranking schizophrenia higher than diabetes on their problem list were more likely "minimalists" and none were "interventionists" or "information seekers". Conclusions: Variations in clinical management encompass multiple clinical actions and physicians subtly shift these decision-making styles depending on patient co-morbidities. Physicians' practice styles may help explain persistent differences in patient care. Training and continuing education efforts to encourage physicians to implement evidence-based clinical practice should account for general styles of decision-making and for how physicians process complicating comorbidities.
    No preview · Article · Mar 2015
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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
    Preview · Article · Nov 2014 · Acta Neuropathologica

  • No preview · Conference Paper · Jun 2014

  • No preview · Conference Paper · Jun 2014
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    Full-text · Article · May 2014 · British Journal of Haematology
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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.
    No preview · Article · Apr 2014
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    ABSTRACT: Background: 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. Objectives: To estimate the effect of patient requests for medications on physician-prescribing behavior, unconfounded by patient, physician, and practice-setting factors. Research Design: Two experiments were conducted among 192 primary care physicians, each using different video-based scenarios: an undiagnosed "patient" with symptoms strongly suggesting sciatica, and a "patient" with already diagnosed chronic knee osteoarthritis. Half of patients with sciatica symptoms requested oxycodone, whereas the other half requested something to help with pain. Similarly, half of knee osteoarthritis patients specifically requested celebrex and half requested something to help with pain. Subjects: To increase generalizability and ensure sufficient numbers were available, we recruited 192 primary care physicians from 6 US states. Measures: The primary outcome was whether physicians would accede to a patient's request for a medication. Alternative pain medications prescribed were secondary outcomes. Results: 19.8% of sciatica patients requesting oxycodone would receive a prescription for oxycodone, compared with 1% of those making no specific request (P = 0.001). Fifty-three percent of knee osteoarthritis patients requesting celebrex would receive it, compared with 24% of patients making no request (P = 0.001). 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). Patients requesting celebrex were much less likely to receive a nonselective nonsteroidal anti-inflammatory drugs (P = 0.008). No patient attributes, physician, or organizational factors influenced a physician's willingness to accede to a patient's medication request. Conclusions: In both scenarios, activated patient requests for a medication substantially affected physician-prescribing decisions, despite the drawbacks of the requested medications.
    No preview · Article · Apr 2014 · Medical Care
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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.
    No preview · Article · Apr 2014 · Medical Care
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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.
    Full-text · Article · Mar 2014 · Quality of Life Research
  • 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.
    No preview · Article · Jan 2014 · British dental journal official journal of the British Dental Association: BDJ online
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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.
    Preview · Article · Jan 2014
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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 (e.g., 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.
    No preview · Article · Nov 2013 · PEDIATRICS
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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.
    No preview · Conference Paper · Nov 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.
    No preview · Conference Paper · Nov 2013

Publication Stats

3k Citations
502.26 Total Impact Points

Institutions

  • 2004-2015
    • New England Research Institutes
      워터타운, Massachusetts, United States
  • 2012
    • Children's Hospital & Research Center Oakland
      Oakland, California, United States
  • 2011
    • Boston Children's Hospital
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2009
    • Harvard Medical School
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2005-2008
    • Harvard University
      Cambridge, Massachusetts, United States