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Methods and processes for the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial

Hertzberg, Vicki; Ingall, Timothy; O'Fallon, William; Asplund, Kjell; Goldfrank, Lewis; Louis, Thomas; Christianson, Teresa
BACKGROUND: Treatment group imbalances in baseline stroke severity in the NINDS intravenous t-PA for acute stroke treatment trial led to controversy regarding the efficacy of tissue plasminogen activator (t-PA) in the treatment of acute ischemic stroke. PURPOSE: Describe the steps used to independently re-evaluate this trial. METHODS: NIH appointed an independent multidisciplinary committee that gained access to the original data. We undertook analyses of t-PA efficacy accounting for this imbalance, as well as analyses to identify subgroups that experienced additional harm or benefit from t-PA. Analyses of time from stroke onset to treatment (OTT), blood pressure, and intracerebral hemorrhage are given as illustrations. RESULTS: Despite subgroup imbalances in baseline stroke severity, when t-PA was administered to acute ischemic stroke patients according to study protocol, there was a statistically significant and clinically important benefit of t-PA treatment resulting in a higher likelihood of having a favorable clinical outcome at 3 months. Moreover, we were unable to identify subgroups of patients between which t-PA treatment effect differed, albeit these analyses had low power. These data failed to support the NINDS investigators' conclusion that effect of t-PA therapy diminished with increasing values of OTT within the protocol-specified 3 h time limit. In addition, the blood pressure measurements were highly variable and inconsistently determined so as to be too unreliable for inclusion in analysis. CONCLUSION: With new NIH requirements for data-sharing, the frequency of re-analysis of clinical trial data may increase substantially. This re-evaluation provides a blueprint for future re-evaluations of other trials. These best practices include re-analysis of the study data, after suitable replication, by an independent multidisciplinary committee, including a skilled statistical programmer analyst. Primary investigators should address significant errors determined in such re-analyses.
PMID: 18697845
ISSN: 1740-7745
CID: 179126

Organization-based incident management: developing a disaster volunteer role on a university campus

Fulmer, Terry; Portelli, Ian; Foltin, George L; Zimmerman, Rae; Chachkes, Esther; Goldfrank, Lewis R
BACKGROUND: Catastrophic events are an ongoing part of life, affecting society both locally and globally. Recruitment, development, and retention of volunteers who offer their knowledge and skills in the event of a disaster are essential to ensuring a functional workforce during catastrophes. These opportunities also address the inherent need for individuals to feel necessary and useful in times of crisis. Universities are a particularly important setting for voluntary action, given that they are based in communities and have access to resources and capabilities to bring to bear on an emergency situation. METHODS: The purpose of the study was to discern how one large private organization might participate and respond in the case of a large scale disaster. Using a 2-phase random sample survey, 337 unique respondents (5.7%) out of a sample of 6000 replied to the survey. RESULTS: These data indicate that volunteers in a private organization are willing to assist in disasters and have skills that can be useful in disaster mitigation. DISCUSSION: Much is to be learned related to the deployment of volunteers during disaster. These findings suggest that volunteers can and will help and that disaster preparedness drills are a logical next step for university-based volunteers.
PMID: 17719508
ISSN: 1540-2495
CID: 156642

Terrorism preparedness

Chapter by: Goldfrank, Lewis; Greller, Howard
in: Environmental and occupational medicine by Rom WN; Markowitz S [Eds]
Philadelphia : Wolters Kluwer/Lippincott Williams & Wilkins, 2007
pp. ?-?
ISBN: 0781762995
CID: 5367

Thermal extremes in the work environment

Chapter by: Delaney, Kathleen A; Goldfrank, Lewis R.
in: Environmental and occupational medicine by Rom WN; Markowitz S [Eds]
Philadelphia : Wolters Kluwer/Lippincott Williams & Wilkins, 2007
pp. ?-?
ISBN: 0781762995
CID: 5373

Goldfrank's manual of toxicologic emergencies

Goldfrank, Lewis R.; Hoffman, Robert S; Nelson, Lewis; Howland, Mary; Lewin, Neal; Flomenbaum, Neal
New York : McGraw-Hill Medical, c2007
Extent: xxiv, 1126 p. : ill. ; 21 cm.
ISBN: 007144310x
CID: 179173

Countering chemical agents

Dart, Richard C; Bevelaqua, Armando; DeAtley, Craig; Sidell, Frederick; Goldfrank, Lewis; Madsen, James; Alcorta, Richard; Keim, Mark; Auf der Heide, Erik; Joyce, Steven; Shannon, Michael; Burgess, Jefferey; Kirk, Mark; Henretig, Fred; Thomas, Richard; Geller, Robert; Bronstein, Alvin C; Eitzen, Edward; Kilbourne, Edwin; Fenton, David; Reisman, Dori; Gum, Robert; Tarosky, Matthew; Edelman, Philip; Erdman, Andrew; Bogdan, Gregory M
PMID: 17169687
ISSN: 0197-2510
CID: 179127

Rewarming rates in urban patients with hypothermia: prediction of underlying infection

Delaney, Kathleen A; Vassallo, Susi U; Larkin, Gregory L; Goldfrank, Lewis R
BACKGROUND: In the urban setting, hypothermia is commonly associated with illness or intoxication, with death often secondary to infection. OBJECTIVES: To evaluate factors that affect the rewarming rate (RWR) and the ability of the RWR and other clinical markers to predict the presence or absence of underlying infection in an adult urban population. METHODS: This was a prospective observational study of hypothermic patient visits to a large emergency department. Serial temperatures were obtained during rewarming to construct rewarming curves. Rewarming modalities selected by emergency physicians were correlated with admission temperatures. Univariate associates of RWR and infection were assessed. RESULTS: The authors identified 96 patient visits. The median temperature was 89.5 degrees F (31.9 degrees C; range, 73.0 degrees F to 95.0 degrees F [22.8 degrees C to 35.0 degrees C]). Thirteen patients had temperatures of < 80.0 degrees F (26.0 degrees C). Seven died within 14 hours of presentation; six, of infection. No patient experienced ventricular fibrillation. Potential candidate predictors of infection from a multivariate analysis were a RWR of < 1.80 degrees F (1.0 degrees C) per hour and a serum albumin of < 2.7 g/dL. Rapid rewarming was associated with the absence of infection and a temperature below 86.0 degrees F (30.0 degrees C). In patients without significant underlying illness, rewarming rates appeared to be independent of the modality of rewarming. CONCLUSIONS: Rewarming rates reflect intrinsic capacity for thermogenesis. Increased RWRs were associated with the absence of infection. The achievement of normothermia did not prevent death in infected patients. Initiation of invasive rewarming in urban patients with hypothermia who have not had hypothermic cardiac arrest may be unwarranted. Management of this population should emphasize support, detection, and treatment of underlying illness
PMID: 16946289
ISSN: 1553-2712
CID: 74008

The interface: ethical decision making, medical toxicology, and emergency medicine

Kreismann, Erica; Gang, Maureen; Goldfrank, Lewis R
The overwhelming social and economic costs of alcohol, tobacco, and other substances of abuse are discussed, as are some of the important public health interventions appropriate for emergency physicians. This article addresses the complexity of ethical decision making when toxicologic emergencies occur in emergency medicine. The management strategies for patients with apparent intoxication are addressed with regard to decision-making capacity. The balance between confidentiality and support for an individual patient and responsibility of the physician to society is discussed. The relative importance of HIPAA is compared with an individual physician's code of ethics
PMID: 16877142
ISSN: 0733-8627
CID: 68408

Initial evaluation of the patient : vital signs and toxic syndromes

Chapter by: Flomenbaum NE; Goldfrank LR; Hoffman RS; Howland MA; Lewin NA; Nelson LS
in: Goldfrank's toxicologic emergencies by Goldfrank, Lewis R; Flomenbaum, Neal [Eds]
New York : McGraw-Hill Medical, 2006
pp. 37-41
ISBN: 0071437630
CID: 4542

Principles of managing the poisoned or overdosed patient

Chapter by: Flomenbaum NE; Goldfrank LR; Hoffman RS; Howland MA; Lewin NA; Nelson LS
in: Goldfrank's toxicologic emergencies by Goldfrank, Lewis R; Flomenbaum, Neal [Eds]
New York : McGraw-Hill Medical, 2006
pp. 42-50
ISBN: 0071437630
CID: 4541