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Biomedical subjects

Brian Schwartz

Publications and source records attributed to Brian Schwartz.

At least 19 recordsLinked to original sources
PubMed2007

Sorafenib in advanced clear-cell renal-cell carcinoma.

BACKGROUND: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma. METHODS: From November 2003 to March 2005, we randomly assigned 903 patients with renal-cell carcinoma that was resistant to standard therapy to receive either continuous treatment with oral sorafenib (at a dose of 400 mg twice daily) or placebo; 451 patients received sorafenib and 452 received placebo. The primary end point was overall survival. A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo. Consequently, crossover was permitted from placebo to sorafenib, beginning in May 2005. RESULTS: At the January 2005 cutoff, the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group (hazard ratio for disease progression in the sorafenib group, 0.44; 95% confidence interval [CI], 0.35 to 0.55; P<0.01). The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death, as compared with placebo (hazard ratio, 0.72; 95% CI, 0.54 to 0.94; P=0.02), although this benefit was not statistically significant according to the O'Brien-Fleming threshold. Partial responses were reported as the best response in 10% of patients receiving sorafenib and in 2% of those receiving placebo (P<0.001). Diarrhea, rash, fatigue, and hand-foot skin reactions were the most common adverse events associated with sorafenib. Hypertension and cardiac ischemia were rare serious adverse events that were more common in patients receiving sorafenib than in those receiving placebo. CONCLUSIONS: As compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; however, treatment is associated with increased toxic effects. (ClinicalTrials.gov number, NCT00073307 [ClinicalTrials.gov].).

Adult↗
PubMed2006

To predict progression-free survival and overall survival in metastatic renal cancer treated with sorafenib: pilot study using dynamic contrast-enhanced Doppler ultrasound.

INTRODUCTION: The objective of this study was to evaluate dynamic contrast-enhanced Doppler ultrasound (DCE-US) with perfusion software (Vascular Recognition Imaging) and contrast agent injection as a predictor of tumour response, progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: Thirty patients with a metastatic renal cell carcinoma (RCC) already enrolled in a double-blind randomised study were evaluated. Examinations were performed at baseline, and after 3 and 6 weeks on sorafenib or a placebo in patients with tumour targets that were accessible to DCE-US. RESULTS: A total of 85 examinations were performed, 30 at baseline, 28 at 3 weeks and 27 at 6 weeks. The combination of a decrease in contrast uptake exceeding 10% and stability or a decrease in tumour volume allowed us to discriminate seven good responders and 20 poor responders at 3 weeks. There was a statistically significant difference in PFS (p=10(-4)) and OS (p=10(-4)) between good and poor responders. CONCLUSION: DCE-US is a new noninvasive imaging technique which might be an effective tool for evaluating antiangiogenic drugs in renal cancer.

Adult↗
PubMed2006

Phase II study of sorafenib in patients with advanced hepatocellular carcinoma.

PURPOSE: This phase II study of sorafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, assessed efficacy, toxicity, pharmacokinetics, and biomarkers in advanced hepatocellular carcinoma (HCC) patients. METHODS: Patients with inoperable HCC, no prior systemic treatment, and Child-Pugh (CP) A or B, received continuous, oral sorafenib 400 mg bid in 4-week cycles. Tumor response was assessed every two cycles using modified WHO criteria. Sorafenib pharmacokinetics were measured in plasma samples. Biomarker analysis included phosphorylated extracellular signal regulated kinase (pERK) in pretreatment biopsies (immunohistochemistry) and blood-cell RNA expression patterns in selected patients. RESULTS: Of 137 patients treated (male, 71%; median age, 69 years), 72% had CP A, and 28% had CP B. On the basis of independent assessment, three (2.2%) patients achieved a partial response, eight (5.8%) had a minor response, and 46 (33.6%) had stable disease for at least 16 weeks. Investigator-assessed median time to progression (TTP) was 4.2 months, and median overall survival was 9.2 months. Grade 3/4 drug-related toxicities included fatigue (9.5%), diarrhea (8.0%), and hand-foot skin reaction (5.1%). There were no significant pharmacokinetic differences between CP A and B patients. Pretreatment tumor pERK levels correlated with TTP. A panel of 18 expressed genes was identified that distinguished "nonprogressors" from "progressors" with an estimated 100% accuracy. CONCLUSION: Although single-agent sorafenib has modest efficacy in HCC, the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents.

Adult↗
PubMed2006

Comparison of the medical priority dispatch system to an out-of-hospital patient acuity score.

BACKGROUND: Although the Medical Priority Dispatch System (MPDS) is widely used by emergency medical services (EMS) dispatchers to determine dispatch priority, there is little evidence that it reflects patient acuity. The Canadian Triage and Acuity Scale (CTAS) is a standard patient acuity scale widely used by Canadian emergency departments and EMS systems to prioritize patient care requirements. OBJECTIVES: To determine the relationship between MPDS dispatch priority and out-of-hospital CTAS. METHODS: All emergency calls on a large urban EMS communications database for a one-year period were obtained. Duplicate calls, nonemergency transfers, and canceled calls were excluded. Sensitivity and specificity to detect high-acuity illness, as well as positive predictive value (PPV) and negative predictive value (NPV), were calculated for all protocols. RESULTS: Of 197,882 calls, 102,582 met inclusion criteria. The overall sensitivity of MPDS was 68.2% (95% confidence interval [CI] = 67.8% to 68.5%), with a specificity of 66.2% (95% CI = 65.7% to 66.7%). The most sensitive protocol for detecting high acuity of illness was the breathing-problem protocol, with a sensitivity of 100.0% (95% CI = 99.9% to 100.0%), whereas the most specific protocol was the one for psychiatric problems, with a specificity of 98.1% (95% CI = 97.5% to 98.7%). The cardiac-arrest protocol had the highest PPV (92.6%, 95% CI = 90.3% to 94.3%), whereas the convulsions protocol had the highest NPV (85.9%, 95% CI = 84.5% to 87.2%). The best-performing protocol overall was the cardiac-arrest protocol, and the protocol with the overall poorest performance was the one for unknown problems. Sixteen of the 32 protocols performed no better than chance alone at identifying high-acuity patients. CONCLUSIONS: The Medical Priority Dispatch System exhibits at least moderate sensitivity and specificity for detecting high acuity of illness or injury. This performance analysis may be used to identify target protocols for future improvements.

Clinical Protocols↗
PubMed2006

Bone mineral density in the complete androgen insensitivity and 5alpha-reductase-2 deficiency syndromes.

CONTEXT: Subjects with complete androgen insensitivity (CAI) and 5alpha-reductase-2 deficiency (5alphaRD-2) are natural human models to study the direct effect of androgens on bone mineral density (BMD). OBJECTIVE: The objective of this study was to test the hypothesis that androgens have a direct effect on BMD in men. DESIGN: This was a prospective, observational study (1989-1999) using dual energy x-ray absorptiometry. SETTING: The study was set in an outpatient specialty referral center. PATIENTS OR OTHER PARTICIPANTS: All known subjects with these conditions (12 CAI and 16 5alphaRD-2) from diverse sociodemographic backgrounds were recruited for the study. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURE: Mean Z score and weight-matched Z score at lumbar spine and femoral neck for CAI and 5alphaRD-2 subjects were determined. RESULTS: Twelve CAI subjects had mean Z score at L2-L4 of -2.84 (+/-0.97, P < 0.001) and a mean weight-matched Z score of -2.52 (+/-0.94, P < 0.001). The mean Z score at the femoral neck was -1.33 (+/-0.91, P < 0.001) and the mean weight-matched Z score was -1.10 (+/-0.82, P = 0.001). Sixteen 5alphaRD-2 subjects had a mean Z score at L2-L4 of -0.84 (+/-1.29, P = 0.02) and a mean weight-matched Z score for 15 of 16 patients of -0.44 (+/-1.08, P = 0.14). The mean Z score at the femoral neck was 0.14 (+/-1.02, P = 0.58) and the mean weight-matched Z score for 15 of 16 patients was 0.49 (+/-0.94, P = 0.06). Therefore, in CAI subjects, BMD was significantly decreased in the spine and hip. 5alphaRD-2 subjects had normal BMD values. CONCLUSIONS: 1) Androgens are of direct importance in the development and/or maintenance of BMD; and 2) testosterone and/or low levels of dihydrotestosterone appear to be sufficient for BMD development and/or maintenance.

Absorptiometry, Photon↗
PubMed2006

Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma.

PURPOSE: This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients initially received oral sorafenib 400 mg twice daily during the initial run-in period. After 12 weeks, patients with changes in bidimensional tumor measurements that were less than 25% from baseline were randomly assigned to sorafenib or placebo for an additional 12 weeks; patients with > or = 25% tumor shrinkage continued open-label sorafenib; patients with > or = 25% tumor growth discontinued treatment. The primary end point was the percentage of randomly assigned patients remaining progression free at 24 weeks after the initiation of sorafenib. RESULTS: Of 202 patients treated during the run-in period, 73 patients had tumor shrinkage of > or = 25%. Sixty-five patients with stable disease at 12 weeks were randomly assigned to sorafenib (n = 32) or placebo (n = 33). At 24 weeks, 50% of the sorafenib-treated patients were progression free versus 18% of the placebo-treated patients (P = .0077). Median progression-free survival (PFS) from randomization was significantly longer with sorafenib (24 weeks) than placebo (6 weeks; P = .0087). Median overall PFS was 29 weeks for the entire renal cell carcinoma population (n = 202). Sorafenib was readministered in 28 patients whose disease progressed on placebo; these patients continued on sorafenib until further progression, for a median of 24 weeks. Common adverse events were skin rash/desquamation, hand-foot skin reaction, and fatigue; 9% of patients discontinued therapy, and no patients died from toxicity. CONCLUSION: Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy.

Administration, Oral↗
PubMed2006

Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer.

BACKGROUND: With its potent inhibitory effects against Raf-1 kinase and vascular endothelial growth factor receptor-2, sorafenib is a novel oral anticancer agent targeting signal transduction and angiogenic pathways. This study is designed to combine sorafenib and gemcitabine due to their compatibility in preclinical models and nonoverlapping clinical toxicities. EXPERIMENTAL DESIGN: An initial dose-escalation part of the study enrolled patients with advanced solid tumors, followed by an expanded cohort at the recommended dose for patients with advanced unresectable or metastatic pancreatic cancer. Sorafenib is administered continuously, whereas gemcitabine is given at 1,000 mg/m2 weekly x 7 followed by 1 rest week, then weekly x 3 every 4 weeks. RESULTS: Forty-two patients have been enrolled overall, including 19 in the dose-escalation part and 23 in the extended pancreatic cancer cohort. Demographics were as follows: male-to-female ratio = 26:16; median age = 61 years (range 39-83 years); Eastern Cooperative Oncology Group performance status 0:1:2 ratio = 16:21:5. The recommended dose of this combination is sorafenib 400 mg twice daily and gemcitabine 1,000 mg/m2. The most frequent grade 3 or 4 adverse events of all causalities were thrombocytopenia (28.6%), lymphopenia (21.4%), lipase elevation (19%), neutropenia (16.7%), and fatigue (14.3%). Antitumor activity was observed in both groups, with 2 (10.5%) confirmed partial responses in ovarian cancer and 12 patients (63.2%) with disease stabilization in the dose-escalation part; 13 patients (56.5%) achieved disease stabilization in the pancreatic cohort. There was no consistent pharmacokinetic drug-to-drug interaction between sorafenib and gemcitabine. CONCLUSIONS: Sorafenib and gemcitabine are well tolerated in combination; further evaluations in pancreatic and ovarian cancers are warranted.

Adult↗
PubMed2006

Discovery and development of sorafenib: a multikinase inhibitor for treating cancer.

Since the molecular revolution of the 1980s, knowledge of the aetiology of cancer has increased considerably, which has led to the discovery and development of targeted therapies tailored to inhibit cancer-specific pathways. The introduction and refinement of rapid, high-throughput screening technologies over the past decade has greatly facilitated this targeted discovery and development process. Here, we describe the discovery and continuing development of sorafenib (previously known as BAY 43-9006), the first oral multikinase inhibitor that targets Raf and affects tumour signalling and the tumour vasculature. The discovery cycle of sorafenib (Nexavar; Bayer Pharmaceuticals) - from initial screening for a lead compound to FDA approval for the treatment of advanced renal cell carcinoma in December 2005 - was completed in just 11 years, with approval being received approximately 5 years after the initiation of the first Phase I trial.

Animals↗
PubMed2006

Predictors of blood mercury levels in older urban residents.

OBJECTIVE: The objective of this study was to describe the distribution and predictors of blood mercury levels in an adult population. METHODS: This was a cross-sectional analysis of first-visit data (2001-2002) on a random sample of 474 subjects from the Baltimore Memory Study. RESULTS: After adjustment for race/ethnicity, education, assets, and diabetes, persons in the highest quartile of fish consumption had median mercury levels 1.82 times above the levels in the lowest quartile, while those in the highest education category had median mercury levels 1.57 times higher than levels in the lowest category. Nine percent of subjects were above the reference dose recommended by the Environmental Protection Agency, which is high compared with that found by the Centers for Disease Control and Prevention in women of childbearing age. CONCLUSIONS: These findings offer guidance for targeted education and possible new insights regarding the kinetics of mercury.

Aged↗
PubMed2005

Migration of an amplatzer septal occluder device for closure of atrial septal defect into the ascending aorta with formation of an aorta-to-right atrial fistula.

The percutaneous closure of atrial septal defects is increasingly used. Serious complications of the procedure, such as cardiac perforation and tamponade, are rare and usually occur <72 hours after device placement. The investigators report the late development of the erosion of an Amplatzer septal occluder into the ascending aorta with associated aortic-to-right atrial fistula formation.

Adult↗
PubMed2005

Blood mercury levels and neurobehavioral function.

CONTEXT: Due to its cardiovascular benefits, fish consumption is widely encouraged among older Americans. However, this fast-growing population is at increased risk of cognitive impairment and may be particularly sensitive to methylmercury, a neurotoxicant found in fish. OBJECTIVE: To describe associations of blood mercury levels with neurobehavioral test scores in an urban adult population. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis to determine the effect of mercury levels on neurobehavior in 474 randomly selected participants in the Baltimore Memory Study, a longitudinal study of cognitive decline involving 1140 Baltimore residents aged 50 to 70 years. We measured total mercury in whole blood samples and used multiple linear regression to examine its associations with neurobehavioral test scores. First-visit data were obtained in 2001-2002. MAIN OUTCOME MEASURES: Twenty scores from 12 neurobehavioral tests. RESULTS: The median blood mercury level was 2.1 microg/L (range, 0-16 microg/L). After adjustment for covariates, increasing blood mercury was associated with worse performance on Rey complex figure delayed recall, a test of visual memory (beta, -0.224; 95% confidence interval, -0.402 to -0.047). However, increasing blood mercury levels were associated with better performance on finger tapping, a test of manual dexterity (beta for dominant hand, 0.351; 95% confidence interval, 0.017-0.686). CONCLUSION: Overall, the data do not provide strong evidence that blood mercury levels are associated with worse neurobehavioral performance in this population of older urban adults.

Adult↗
PubMed2005

Out-of-hospital cardiac arrest rectilinear biphasic to monophasic damped sine defibrillation waveforms with advanced life support intervention trial (ORBIT).

BACKGROUND: Although biphasic defibrillation waveforms appear to be superior to monophasic waveforms in terminating VF, their relative benefits in out-of-hospital resuscitation are incompletely understood. Prior comparisons of defibrillation waveform efficacy in out-of-hospital cardiac arrest (OHCA) are confined to patients presenting in a shockable rhythm and resuscitated by first responder (basic life support). This effectiveness study compared monophasic and biphasic defibrillation waveform for conversion of ventricular arrhythmias in all OHCA treated with advance life support (ALS). METHODS AND RESULTS: This prospective randomized controlled trial compared the rectilinear biphasic (RLB) waveform with the monophasic damped sine (MDS) waveform, using step-up energy levels. The study enrolled OHCA patients requiring at least one shock delivered by ALS providers, regardless of initial presenting rhythm. Shock success was defined as conversion at 5s to organized rhythm after one to three escalating shocks. We report efficacy results for the cohort of patients treated by ALS paramedics who presented with an initially shockable rhythm who had not received a shock from a first responder (MDS: n=83; RLB: n=86). Shock success within the first three ascending energy shocks for RLB (120, 150, 200J) was superior to MDS (200, 300, 360J) for patients initially presenting in a shockable rhythm (52% versus 34%, p=0.01). First shock conversion was 23% and12%, for RLB and MDS, respectively (p=0.07). There were no significant differences in return of spontaneous circulation (47% versus 47%), survival to 24h (31% versus 27%), and survival to discharge (9% versus 7%). Mean 24h survival rates of bystander witnessed events showed differences between waveforms in the early circulatory phase at 4-10 min post event (mean (S.D.) RLB 0.45 (0.07) versus MDS 0.31 (0.06), p=0.0002) and demonstrated decline as time to first shock increased to 20 min. CONCLUSION: Shock success to an organized rhythm comparing step-up protocol for energy settings demonstrated the RLB waveform was superior to MDS in ALS treatment of OHCA. Survival rates for both waveforms are consistent with current theories on the circulatory and metabolic phases of out-of-hospital cardiac arrest.

Adult↗
PubMed2005

Results of a phase I trial of sorafenib (BAY 43-9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer.

BACKGROUND: Sorafenib (BAY 43-9006), a multiple kinase inhibitor, has been shown to inhibit tumor growth and tumor angiogenesis by targeting Raf kinase, vascular endothelial growth factor receptor, and platelet-derived growth factor receptor. In phase I studies, sorafenib demonstrated single-agent activity in patients with advanced solid tumors and was successfully combined with oxaliplatin in preclinical studies. This phase I study investigated the safety, pharmacokinetics, and efficacy of sorafenib in combination with oxaliplatin. PATIENTS AND METHODS: Twenty-seven patients with refractory solid tumors were enrolled in the initial dose-escalation part (cohorts 1, 2A, and 2B) and 10 additional patients with oxaliplatin-refractory colorectal cancer were subsequently enrolled in an extension part (cohort 3). Oxaliplatin 130 mg/m2 was given on day 1 of a 3-week cycle and oral sorafenib was administered continuously from day 4 of cycle 1 at 200 mg twice daily (cohort 1) or 400 mg twice daily (cohorts 2A, 2B, and 3). RESULTS: Adverse events were generally mild to moderate and the maximum tolerated dose was not reached. Common adverse events were diarrhea (52% of patients in the dose-escalation part and 20% in the extension part), sensory neuropathy (44% and 20%), and dermatologic toxicities (41% and 80%). No pharmacokinetic interaction between sorafenib and oxaliplatin was detectable. Two patients with gastric cancer had a partial response. Forty-three percent of patients in cohorts 1 and 2A/B and 78% of patients in cohort 3 exhibited stable disease for >or=10 weeks. CONCLUSION: Continuous oral sorafenib 400 mg twice daily was safely combined with oxaliplatin without detectable drug interactions and showed preliminary antitumor activity in this phase I study. This dose is recommended for phase II studies.

Administration, Oral↗
PubMed2004

Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors.

PURPOSE: BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor inhibitor that inhibits tumor cell proliferation and angiogenesis. This study established the safety and pharmacokinetics of BAY 43-9006 in 69 patients with advanced refractory solid tumors. PATIENTS AND METHODS: BAY 43-9006 (50 to 800 mg) was administered once or twice daily on a varying weekly schedule. Pharmacokinetic sampling was performed in all patients; preliminary tumor response was also assessed. The effect of BAY 43-9006 on phorbol myristate acetate-stimulated ERK phosphorylation in peripheral blood lymphocytes was studied using flow cytometry. RESULTS: Mild to moderate diarrhea was the most common (55%) treatment-related adverse event. The maximum-tolerated dose was 400 mg bid continuous. Dose-limiting toxicities were grade 3 diarrhea and fatigue at 800 mg bid, and grade 3 skin toxicity at 600 mg bid. BAY 43-9006 pharmacokinetics were highly variable for single and multiple dosing, and toxicity did not appear to be dose dependent. Significant decreases of phorbol myristate acetate-stimulated ERK phosphorylation (P < .01) were identified at doses >/= 200 mg bid continuous. Forty-five patients were assessable for efficacy; one patient had a partial response (hepatocellular carcinoma at 400 mg bid continuous), 25 patients had stable disease, with eight lasting > 6 months and five for >12 months. Eighteen patients had progressive disease, and tumor response could not be evaluated in one patient. CONCLUSION: Oral BAY 43-9006 was well tolerated and appeared to provide some clinical benefits. Based on the results of this study, BAY 43-9006 at 400 mg bid continuous is recommended for ongoing and future studies.

Adolescent↗
PubMed2004

Incremental effectiveness of amlodipine besylate in the treatment of hypertension with single and multiple medication regimens.

BACKGROUND: The objective of this retrospective observational analysis is to examine the clinical effectiveness of amlodipine besylate as monotherapy or in combination with other antihypertensive drugs (AHDs) in systolic blood pressure (BP) control and BP goal attainment, according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) 6, JNC 7, and American Diabetes Association (ADA)recommendations, within a multicenter ambulatory care setting. METHODS: Hypertensive adults (n = 1175) were identified during a 4-year period (1998 to 2001) from a large commercially available electronic medical record (EMR) database. Patients were required to have initiated therapy with amlodipine and have at least one BP measurement within 6 months before, and 12 months after, the medication start date. Patients were divided into cohorts based on the number of AHDs used before, and continued through, the initiation of amlodipine. Mean change in systolic BP was compared from pre- to post-amlodipine, and adjusted change in systolic BP was calculated using multivariate regression. The percentage of patients attaining BP goal was also calculated. RESULTS: In the order of increasing number of AHDs before initiation of amlodipine (0, 1, 2, > or = 3 previous AHDs): adjusted systolic BP change in mm Hg was -16.1 (95% confidence interval [CI]: -17.9, -14.3), -17.6 (95% CI: -19.6, -15.5), -16.7 (95% CI: -19.0, -14.5), and -15.7 (95% CI: -18.7, -12.8), respectively; BP goal attainment was 39%, 45%, 41%, and 45%, respectively. Amlodipine initiation in all regimens showed statistically significant incremental systolic BP reduction and BP goal attainment from baseline (P < .001). CONCLUSIONS: This study suggests that amlodipine besylate is effective alone or as an add-on therapy to diverse classes of agents.

Aged↗
PubMed2004

Evaluating the impact of an educational intervention on documentation of decision-making capacity in an emergency medical services system.

OBJECTIVES: To compare the documentation of decision-making capacity by advanced life support (ALS) providers and signature acquisition before, one month after, and one year after an educational intervention. METHODS: The intervention comprised a one-and-a-half-hour module on assessment and documentation of decision-making capacity. Ambulance call reports were reviewed for all ALS calls occurring during three two-month periods, and refusals of transport were recorded. Provider compliance with documentation of decision-making capacity and signature acquisition were determined from a convenience sample of 75 reports from each period. Reviewers were blinded to study period. Twenty-percent double data entry was undertaken to evaluate accuracy. Ninety-five percent confidence intervals were calculated to compare frequencies of cancelled calls and documentation. RESULTS: From the emergency medical services database, 7,744 calls before the intervention, 7,444 immediately after, and 7,604 one year later were identified. Documentation rates in the second and third periods did not differ from that prior to the intervention (1.3% vs. 0.0% and 0.0% in subsequent periods), nor did the rates of signature acquisition differ (85.3% vs. 85.3% and 78.6%). The accuracy of data entry was 92.6%. However, the frequency of call refusals decreased significantly after the intervention (from 9.0% to 2.0% and 6.6% in the respective periods). CONCLUSIONS: An educational intervention resulted in no change in the rate of decision-making capacity documentation or signature acquisition by ALS providers for refusal of transport. There was a temporary increase in the number of transported patients.

Consent Forms↗
PubMed2004

Clinical variables associated with mortality in out-of-hospital patients with hemodynamically significant bradycardia.

OBJECTIVES: To estimate mortality rates and identify clinical variables associated with mortality among patients with hemodynamically unstable bradycardia in an urban emergency medical services (EMS) system. METHODS: This was a retrospective study conducted in a large, urban EMS system. Adult non-cardiac arrest patients transported by advanced life support paramedics from March 1996 to February 1997 with a heart rate < or =60 beats/min and systolic blood pressure < or =90 mm Hg were included. Transcutaneous pacing was not available. Patients under age 18 years, pregnant, or presenting with vital signs absent were excluded from the study population. Multivariate analysis of the association of patient characteristics with 30-day mortality was conducted by using a Cox proportional hazards model. RESULTS: Of the 247 patients studied, 133 (53.9%) received a fluid bolus, 37 (15.0%) were treated with atropine, and 17 (6.9%) received dopamine. Fifty-one (20.7%) died in the 19-month follow-up period (15.6 per 100 person-years); 10.5% died on the same day, 15.8% within 30 days, and 17.8% within one year. Variables associated with 30-day mortality included wide QRS complex (adjusted risk ratio [RR] 2.6 [95% confidence interval (95% CI) = 1.3 to 5.2]), use of heart rate-lowering calcium channel blockers (adjusted RR 2.1 [95% CI = 1.0 to 4.7]), and paramedic assessment of lack of patient improvement over the course of the call (adjusted RR 0.2 [95% CI = 0.1 to 0.6]). CONCLUSIONS: Out-of-hospital patients with hemodynamically unstable bradycardia have a high mortality rate. A wide QRS complex and use of heart rate-lowering calcium channel blockers were associated with 30-day mortality.

Aged↗