Quantitative brain MRI morphology in severe and attenuated forms of mucopolysaccharidosis type I.

OBJECTIVE: To assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition. METHODS: Brain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4-25 years, enrolled under the study protocol NCT01870375, were compared to 98 healthy controls. RESULTS: Cortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC. Thicker cortex, lower white matter and corpus callosum volumes were already present at the youngest MPS I participants aged 4-5 years. Age-related differences were observed in both MPS I groups, but most markedly in MPS IH, particularly in cortical gray matter metrics. IQ scores were inversely associated with ventricular volume in both MPS I groups and were positively associated with cortical thickness only in MPS IA. CONCLUSIONS: Quantitatively-derived MRI measures distinguished MPS I participants from HC as well as severe from attenuated forms. Age-related neurodevelopmental trajectories in both MPS I forms differed from HC. The extent to which brain structure is altered by disease, potentially spared by treatment, and how it relates to neurocognitive dysfunction needs further exploration.

Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: A review of the literature.

Sensitive, reliable measurement instruments are critical for the evaluation of disease progression and new treatments that affect the brain in the mucopolysaccharidoses (MPS). MPS I, II, and III have early onset clinical phenotypes that affect the brain during development and result in devastating cognitive decline and ultimately death without treatment. Comparisons of outcomes are hindered by diverse protocols and approaches to assessment including applicability to international trials necessary in rare diseases. We review both cognitive and adaptive measures with the goal of providing evidence to a Delphi panel to come to a consensus about recommendations for clinical trials for various age groups. The results of the consensus panel are reported in an accompanying article. The following data were gathered (from internet resources and from test manuals) for each measure and summarized in the discussion: reliability, validity, date and adequacy of normative data, applicability of the measure's metrics, cross cultural validity including translations and adaptations, feasibility in the MPS population, familiarity to sites, sensitivity to change, and interpretability. If, resulting from this consensus, standard protocols are used for both natural history and treatment studies, patients, their families, and health care providers will benefit from the ability to compare study outcomes.

Assessments of neurocognitive and behavioral function in the mucopolysaccharidoses.

The mucopolysaccharidoses (MPS) are a group of rare, inherited lysosomal storage disorders in which accumulation of glycosaminoglycans (GAGs) leads to progressive tissue and organ dysfunction. In addition to a variety of somatic signs and symptoms, patients with rapidly progressing MPS I (Hurler), II, III, and VII can present with significant neurological manifestations, including impaired cognitive abilities, difficulties in language and speech, behavioral abnormalities, sleep problems, and/or seizures. Neurological symptoms have a substantial impact on the quality of life of MPS patients and their families. Due to the progressive nature of cognitive impairment in these MPS patients, neurocognitive function is a sensitive indicator of disease progression, and a relevant outcome when testing efficacy of therapies for these disorders. In order to effectively manage and develop therapies that address neurological manifestations of MPS, it is important to use appropriate neurocognitive assessment tools that are sensitive to changes in neurocognitive function in MPS patients. This review discusses expert opinions on key issues and considerations for effective neurocognitive testing in MPS patients. In addition, it describes the neurocognitive assessment tools that have been used in clinical practice for these patients. The content of this review is based on existing literature and information from a meeting of international experts with extensive experience in managing and treating MPS disorders.

Neurocognitive clinical outcome assessments for inborn errors of metabolism and other rare conditions.

Well-defined and reliable clinical outcome assessments are essential for determining whether a drug provides clinically meaningful treatment benefit for patients. In 2015, FDA convened a workshop, "Assessing Neurocognitive Outcomes in Inborn Errors of Metabolism." Topics covered included special challenges of clinical studies of inborn errors of metabolism (IEMs) and other rare diseases; complexities of identifying treatment effects in the context of the dynamic processes of child development and disease progression; and the importance of natural history studies. Clinicians, parents/caregivers, and participants from industry, academia, and government discussed factors to consider when developing measures to assess treatment outcomes, as well as tools and methods that may contribute to standardizing measures. Many issues examined are relevant to the broader field of rare diseases in addition to specifics of IEMs.

A Prospective Natural History Study of Mucopolysaccharidosis Type IIIA.

OBJECTIVES: To characterize the clinical course of mucopolysaccharidosis type IIIA (MPS IIIA), and identify potential endpoints for future treatment trials. STUDY DESIGN: Children with a confirmed diagnosis of MPS IIIA, functioning above a developmental age of 1 year, were followed for up to 2 years. Cognitive status and brain atrophy were assessed by standardized tests and volumetric magnetic resonance imaging, respectively. Liver and spleen volumes and cerebrospinal fluid and urine biomarker levels were measured. RESULTS: Twenty-five children, from 1.1 to 18.4 years old, were enrolled, and 24 followed for at least 12 months. 19 exhibited a rapidly progressing (RP) form of MPS IIIA, and 5, a more slowly progressing form. Children with RP plateaued in development by 30 months, followed by rapid regression after 40-50 months. In patients with RP, cognitive developmental quotients showed consistent steep declines associated with progressive cortical gray matter atrophy. Children with slowly progressing had a similar but more prolonged course. Liver and spleen volumes were approximately double normal size, and cerebrospinal fluid and urine heparin sulfate levels were elevated and relatively constant over time. CONCLUSION: Developmental quotient and cortical gray matter volume are sensitive markers of disease progression in MPS IIIA, and may have utility as clinical endpoints in treatment trials. For optimal outcomes, treatment may need to be instituted in children before the onset of steep cognitive decline and brain atrophy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01047306.

Roles of disease severity and post-discharge outpatient visits as predictors of hospital readmissions.

BACKGROUND: Risks prediction models of 30-day all-cause hospital readmissions are multi-factorial. Severity of illness (SOI) and risk of mortality (ROM) categorized by All Patient Refined Diagnosis Related Groups (APR-DRG) seem to predict hospital readmission but lack large sample validation. Effects of risk reduction interventions including providing post-discharge outpatient visits remain uncertain. We aim to determine the accuracy of using SOI and ROM to predict readmission and further investigate the role of outpatient visits in association with hospital readmission. METHODS: Hospital readmission data were reviewed retrospectively from September 2012 through June 2015. Patient demographics and clinical variables including insurance type, homeless status, substance abuse, psychiatric problems, length of stay, SOI, ROM, ICD-10 diagnoses and medications prescribed at discharge, and prescription ratio at discharge (number of medications prescribed divided by number of ICD-10 diagnoses) were analyzed using logistic regression. Relationships among SOI, type of hospital visits, time between hospital visits, and readmissions were also investigated. RESULTS: A total of 6011 readmissions occurred from 55,532 index admissions. The adjusted odds ratios of SOI and ROM predicting readmissions were 1.31 (SOI: 95 % CI 1.25-1.38) and 1.09 (ROM: 95 % CI 1.05-1.14) separately. Ninety percent (5381/6011) of patients were readmitted from the Emergency Department (ED) or Urgent Care Center (UCC). Average time interval from index discharge date to ED/UCC visit was 9 days in both the no readmission and readmission groups (p > 0.05). Similar hospital readmission rates were noted during the first 10 days from index discharge regardless of whether post-index discharge patient clinic visits occurred when time-to-event analysis was performed. CONCLUSIONS: SOI and ROM significantly predict hospital readmission risk in general. Most readmissions occurred among patients presenting for ED/UCC visits after index discharge. Simply providing early post-discharge follow-up clinic visits does not seem to prevent hospital readmissions.

Quantifying behaviors of children with Sanfilippo syndrome: the Sanfilippo Behavior Rating Scale.

The Sanfilippo Behavior Rating Scale (SBRS), a 68 item questionnaire, has been developed to assess the behavioral phenotype of children with Sanfilippo syndrome and its progression over time. Fifteen scales rate orality, movement/activity, attention/self-control, emotional function including anger and fear, and social interaction. Items within scales intercorrelate; measures of internal consistency are adequate. Twelve scales are grouped into 4 abnormality clusters: Movement, Lack of fear, Social/emotional and Executive Dysfunction. A Loess age-trajectory analysis showed that Lack of Fear, Social/Emotional and Executive Dysfunction increased steadily with age; Orality and Mood/Anger/Aggression leveled off. Movement peaked around 6years, then declined as children's excessive/purposeless actions stopped. Compared with standard scales, SBRS Movement was appropriately associated with the Vineland Motor scale; SBRS Lack of Fear had significant associations with the Autism Diagnostic Observation Schedule (ADOS), indicating a symptom overlap between Sanfilippo syndrome and autism. This suggests that reduced fearfulness may be the most salient/sensitive SBRS marker of disease progression. Volumetric MRI showed that increased Lack of Fear was significantly associated with reduced amygdala volume, consistent with our hypothesis that the behavior seen in Sanfilippo syndrome is a variant of Klüver-Bucy syndrome. Hippocampal volume loss had twice the effect on Social-Emotional Dysfunction as amygdala loss, consistent with a hippocampal role in attachment and social emotions. In conclusion, the SBRS assesses the Sanfilippo behavioral phenotype; it can measure behavior change that accompanies disease progression and/or results from treatment.

Using the LACE index to predict hospital readmissions in congestive heart failure patients.

BACKGROUND: The LACE index has been used to predict the risk of unplanned readmission within 30 days after hospital discharge in both medical and surgical patients. The aim of this study is to validate the accuracy of using the LACE index in CHF patients. METHODS: This was a retrospective study. The LACE index score was calculated on each patient who was admitted to hospital due to an acute CHF exacerbation. Operational and clinical variables were collected from patients including basic clinical characteristics, length of hospitalization, comorbidities, number of previous ED visits in the past 6 months before the index admission, and the number of post discharge ED revisits at 30, 60, and 90 days. All variables were analyzed by multivariate logistic regression to determine the association between clinical variables and the hospital unplanned readmissions. C-statistic was used to discriminate those patients with high risk of readmissions. RESULTS: Of the 253 patients included in the study, 24.50% (62/253) experienced unplanned readmission to hospital within 30 days after discharge. The LACE index was slightly higher in patients readmitted versus patients not readmitted (12.17 ± 2.22 versus 11.80 ± 1.92, p = 0.199). Adjusted odds ratios based on logistic regression of all clinical variables showed only the number of previous ED visits (OR 1.79, 95% CI 1.30-2.47, p < 0.001), history of myocardial infarction (OR 2.51, 95% CI 1.02-6.21, p = 0.045), and history of peripheral vascular disease (OR 10.75, 95% CI 1.52-75.73, p = 0.017) increased the risk of unplanned readmission within 30 days of hospital discharge. However, patients with high LACE scores (≥10) had a significantly higher rate of ED revisits (15.04% vs 0%) within 30 days from the index discharge than those with low LACE scores (p = 0.030). CONCLUSION: The LACE index may not accurately predict unplanned readmissions within 30 days from hospital discharge in CHF patients. The LACE high risk index may have utility as a screening tool to predict high risk ED revisits after hospital discharge.

Use of RIFLE criteria to predict the severity and prognosis of acute kidney injury in emergency department patients with rhabdomyolysis.

BACKGROUND: RIFLE criteria (Risk, Injury, Failure, Loss, End-stage) have not been evaluated in Emergency Department (ED) patients at risk of acute kidney injury (AKI). AKI occurs in rhabdomyolysis. STUDY OBJECTIVES: To use RIFLE criteria to stratify the severity of AKI and predict prognosis in ED patients with acute rhabdomyolysis. METHODS: This is a retrospective study of consecutive patients with rhabdomyolysis over a 44-month period. Data included ED admission anion gap, blood urea nitrogen (BUN), calcium, phosphate, potassium, urinalysis, toxicology screen, and hematocrit. Creatine kinase, creatinines, and hematocrits were followed serially. Hospital length of stay (LOS) and need for dialysis were also recorded. RESULTS: RIFLE categories were calculated for 135 patients. At admission, 60 (44%) had no AKI, 20 (15%) had Risk, 32 (24%) had Injury, and 23 (17%) had Failure. These categories were significantly associated with increasing magnitude of volume depletion, potassium, phosphate, BUN, and the anion gap. They predicted differences in LOS, dialysis, discharge creatinine, and the rate of normalization of the admission creatinine. Mortality was low (2%), as was morbidity. Only 8/132 surviving patients (6%) were discharged with a creatinine >2 mg/dL. CONCLUSIONS: The RIFLE categories correlated significantly with known markers of rhabdomyolysis and AKI. They also predicted LOS, dialysis, renal morbidity, and the timing of recovery. RIFLE criteria could be used to predict the outcome of ED patients and facilitate admission and discharge decisions.

Psychometric Validation of the Haemo-QOL-A in Participants with Hemophilia A Treated with Gene Therapy.

Purpose: The hemophilia-specific health-related quality of life (HRQOL) questionnaire (Haemo-QOL-A) is validated for detecting QOL changes following standard therapy for hemophilia A, but has not been rigorously evaluated after gene therapy. This post hoc analysis evaluated the psychometric properties of Haemo-QOL-A in adult people with severe hemophilia A (PWSHA) receiving valoctocogene roxaparvovec (AAV5-hFVIII-SQ) in 2 clinical trials (phase 1/2, NCT02576795; phase 3, NCT03370913). Patients and Methods: Adult PWSHA (factor VIII levels ≤1 IU/dL) received 1 AAV5-hFVIII-SQ infusion (6×1013 vg/kg). Participants were assessed using the Haemo-QOL-A and the EuroQOL (EQ)-5D-5L and visual analog scale (VAS) questionnaires pre- and post-infusion. Psychometric analyses included convergent and discriminant validity, internal consistency, and reliability. Clinically important difference (CID) was estimated using 3-point change in EQ-5D-5L VAS as anchor. Results: Haemo-QOL-A data were analyzed from 7 (phase 1/2, 3-year follow-up) and 16 participants (phase 3, 26-week analysis). Change in Haemo-QOL-A Total Scores correlated with EQ-5D-5L VAS score change at 26 weeks (Pearson's correlation 0.77). At 26 weeks, increased Haemo-QOL-A Physical Functioning was associated with decreased EQ-5D-5L Pain and Discomfort and decreased Anxiety and Depression (Spearman's Rank correlations -0.73 and -0.62, respectively, P <0.01). Internal consistency analysis showed good reliability for all domains (Cronbach's alpha >0.7) except Treatment Concern (Cronbach's alpha = 0.31). Anchor-based CID estimates were met for Haemo-QOL-A Total Score (≥5.5) and domain scores (≥6) for Consequences of Bleeding, Physical Functioning, Role Functioning, and Worry. Conclusion: Our preliminary results suggest that the Haemo-QOL-A is a valid, reliable instrument for HRQOL assessment in PWSHA undergoing gene therapy. Future research should be undertaken to confirm these findings in a larger number of participants.

Attention and corpus callosum volumes in individuals with mucopolysaccharidosis type I.

OBJECTIVE: Previous research suggests attention and white matter (WM) abnormalities in individuals with mucopolysaccharidosis type I (MPS I); this cross-sectional comparison is one of the first to examine the relationship of WM structural abnormalities as measured by corpus callosum (CC) volumes with attention scores to evaluate this relationship in a larger sample of patients with MPS I. METHODS: Volumetric MRI data and performance on a computerized measure of sustained attention were compared for 18 participants with the severe form of MPS I (MPS IH), 18 participants with the attenuated form of MPS I (MPS IATT), and 60 typically developing age-matched controls. RESULTS: The MPS I groups showed below-average mean attention scores (p < 0.001) and smaller CC volumes (p < 0.001) than controls. No significant associations were found between attention performance and CC volume for controls. Attention was associated with posterior CC volumes in the participants with MPS IH (p = 0.053) and total (p = 0.007) and anterior (p < 0.001) CC volumes in participants with MPS IATT. CONCLUSIONS: We found that attention and CC volumes were reduced in participants with MPS I compared to typically developing controls. Smaller CC volumes in participants with MPS I were associated with decreased attention; such an association was not seen in controls. While hematopoietic cell transplantation used to treat MPS IH may compound these effects, attention difficulties were also seen in the MPS IATT group, suggesting that disease effects contribute substantially to the clinical attentional difficulties seen in this population.

Treatment delay in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: a key process analysis of patient and program factors.

BACKGROUND: Most hospitals that perform primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in the United States exceed the recommended door-to-balloon time. There is heightened interest in identifying and eliminating factors that introduce delay. METHODS: We performed a key process analysis of our primary PCI program, assessed the relative contribution of individual time intervals on total ischemic time, and identified predictors of delay. RESULTS: Median times and predictors of delay within each time interval were determined for the entire STEMI cohort ("real world") and after exclusion of patients with atypical symptoms and/or presentations of STEMI that resulted in inherent delay in diagnosis and treatment ("ideal world"). Delays in therapy were symptom onset to presentation (120 minutes [interquartile range, IQR, 60-310 minutes, ideal world] and 150 minutes [IQR 60-360 minutes, real world]; predictors of delay were peripheral vascular disease, self-transportation, daytime and weekend presentation); door-to-balloon time (118.5 minutes [IQR 96-141 minutes, ideal world] and 125 minutes [IQR 100-170 minutes, real world]; predictors of delay were female sex, previous stroke, nighttime and weekend presentation, and cardiogenic shock); and symptom onset to first balloon inflation (272 minutes [IQR 187-465 minutes, ideal world] and 297 minutes [IQR 198-560 minutes, real world]; predictors of delay were peripheral vascular disease, weekend presentation, and self-transportation). CONCLUSIONS: Key process analysis of a primary PCI program identifies treatment delays unique to the hospital and the patient population it serves.

Recurrent life-threatening ventricular dysrhythmias associated with acute hydrofluoric acid ingestion: observations in one case and implications for mechanism of toxicity.

INTRODUCTION: Hydrofluoric acid (HF) is a weak inorganic acid used for etching and as rust remover. Systemic toxicity is manifested as ventricular dysrhythmias. The mechanisms for these dysrhythmias are not well elucidated. CASE REPORT: An 82-year-old woman ingested 8 ounces of 7% HF. Shortly after emergency department (ED) arrival, she became pulseless, developing recurrent ventricular dysrhythmias. She was defibrillated 17 times and received several doses of calcium, magnesium, and lidocaine. After three hours, she returned to sustained NSR. She was discharged home after four days. DISCUSSION: The electrocardiographic findings in this patient demonstrate hypocalcemia, which has been implicated as the culprit in HF-induced arrhythmias. However, despite correction of the hypocalcemia, the ventricular arrhythmias persisted. The proposed mechanisms of systemic HF toxicity and the relevant literature are discussed. CONCLUSION: Ventricular dysrhythmias due to HF toxicity seem to be independent of either hypocalcemia or hyperkalemia. Systemic toxicity after ingestions may be delayed and precipitous.

ED ultrasound in hepatobiliary disease.

To evaluate the diagnostic accuracy of gallbladder ultrasound performed by emergency physicians (EPUS) in patients with right upper quadrant (RUQ) and epigastric (EPI) pain, adults>18 years of age with RUQ or EPI pain were prospectively evaluated by physical examination, laboratory data, and EPUS followed by a blinded radiology department ultrasound (RADUS). Diagnostic categories included: "normal gallbladder"; "uncomplicated symptomatic cholelithiasis" (uncomplicated SCL; stones present but symptoms and signs relieved and no abnormal blood-work); or "complicated symptomatic cholelithiasis" (CSCL; stones and positive symptoms and signs including abnormal blood-work). Final Emergency Department patient assessments based on the RADUS were compared to the EPUS. Over 2-years, 127 patients were enrolled. The sensitivity of the EPUS for detecting stones was 94% (positive predictive value 99%; specificity 96%; negative predictive value 73%). In conclusion, the EPUS is a highly sensitive and reliable indicator of the presence of gallstones.

A longitudinal study of emotional adjustment, quality of life and adaptive function in attenuated MPS II.

OBJECTIVES: The behavioral, adaptive and quality of life characteristics of attenuated mucopolysaccharidosis type II (MPS II) have not been well studied. Understanding changes over time in the attenuated phenotype may assist in helping achieve better outcomes in long-term function. This longitudinal study investigates these outcomes in relation to age, somatic disease burden, and IQ. Specifically, somatic disease burden is a major challenge for these patients, even with treatment with enzyme replacement therapy. METHODS: 15 patients, 10 between ages 6 and < 12 and 5 between ages ≥ 12 and 18, were selected who had at least 2 yearly visits. The occurrence of physical signs, the Physical Symptom Score, and IQ in these two groups was studied as well as the longitudinal association of age with standardized measures of quality of life, adaptive function, and behavioral symptoms as rated by parents and the child's self-report. Slopes by age across and within patients were calculated for these measures. RESULTS: All but one child had hearing loss, most had joint contractures and short stature. Somatic disease burden increased with age. IQ, although normal for most, also improved with age in those under 12 years of age. Physical quality of life decreased while psychosocial quality of life increased with age. Although other adaptive skills were in the broad average range, daily living skills were low at baseline relative to normative data and decreased over time. Behavior ratings indicated improvement in attention and hyperactivity over time. No patient had severe psychopathology, but older children reported an increasing sense of inadequacy and low self-esteem on self-report, presumably due to increasing awareness of differences from peers over time. CONCLUSIONS: Attenuated MPS II patients have increasing somatic disease burden and poor physical quality of life as they develop as well as decreasing self-esteem and sense of adequacy. Psychosocial quality of life, adaptive skills, and attention improve. Recognition of and intervention around these issues will be beneficial to MPS II attenuated patients who have the resources to use such assistance to improve their long-term outcomes.

Predictors of mortality among initially stable adult pelvic trauma patients in the US: Data analysis from the National Trauma Data Bank.

OBJECTIVES: Pelvic fractures are associated with increased risk of death among trauma patients. Studies show independent risks predicting mortality among patients with pelvic fractures vary across different geographic regions. This study analyses national data to determine predictors of mortality in initially stable adult pelvic trauma patients in the US. METHODS: This study is a retrospective analysis of the US National Trauma Data Bank from January 2003 to December 2010 among trauma patients ≥18 years of age with pelvic fractures (including acetabulum). Over 150 variables were reviewed and analysed. The primary outcome was all-cause in-hospital mortality. Logistic regression analysis was used to determine independent risk factors predictive of in-hospital mortality in stable pelvic fracture patients. RESULTS: 30,800 patients were included in the final analysis. Overall in-hospital mortality rate was 2.7%. Mortality increased twofold in middle aged patients (age 55-70), and increased nearly fourfold in patients with advanced age ≥70. We found patients with advanced age, higher severity of injury, Glasgow Coma Scale (GCS) <8, GCS between 9 and 12, prolonged mechanical ventilation, and/or in-hospital blood product administration experienced higher mortality. Patients transported to level 1 or level 2 trauma centres experienced lower mortality while concomitantly experiencing higher associated internal injuries. CONCLUSIONS: Geriatric and middle aged pelvic fracture patients experience higher mortality. Predictors of mortality in initially stable pelvic fracture patients are advanced age, injury severity, mental status, prolonged mechanical ventilation, and/or in-hospital blood product administration. These patients might benefit from transport to local level 1 or level 2 trauma centres.

Inadequate analgesia in emergency medicine.

Review of emergency department pain management practices demonstrates pain treatment inconsistency and inadequacy that extends across all demographic groups. This inconsistency and inadequacy appears to stem from a multitude of potentially remediable practical and attitudinal barriers that include (1) a lack of educational emphasis on pain management practices in nursing and medical school curricula and postgraduate training programs; (2) inadequate or nonexistent clinical quality management programs that evaluate pain management; (3) a paucity of rigorous studies of populations with special needs that improve pain management in the emergency department, particularly in geriatric and pediatric patients; (4) clinicians' attitudes toward opioid analgesics that result in inappropriate diagnosis of drug-seeking behavior and inappropriate concern about addiction, even in patients who have obvious acutely painful conditions and request pain relief; (5) inappropriate concerns about the safety of opioids compared with nonsteroidal anti-inflammatory drugs that result in their underuse (opiophobia); (6) unappreciated cultural and sex differences in pain reporting by patients and interpretation of pain reporting by providers; and (7) bias and disbelief of pain reporting according to racial and ethnic stereotyping. This article reviews the literature that describes the prevalence and roots of oligoanalgesia in emergency medicine. It also discusses the regulatory efforts to address the problem and their effect on attitudes within the legal community.

Bedside diagnosis of vertigo: value of the history and neurological examination.

Vertigo is caused by disturbance of the input or central processing of sensory signals from the vestibular apparatus that provide information regarding the position of the body in space. It is caused either by asymmetric disruption of sensory input from the vestibular organs or asymmetric integration of vestibular input into the central nervous system. Vertigo is readily differentiated from other causes of dizziness by a sensation of motion. A crucial aspect of the management of the emergency department patient with vertigo is the differentiation of vertigo associated with acute stroke syndromes from vertigo due to peripheral causes. Routine computerized axial tomography imaging is insensitive for posterior circulation strokes, so for emergency physicians, the history and neurological examination remain the most useful diagnostic tools. This article emphasizes the history and physical examination in the localization of the lesion in patients with vertigo and offers a rational basis for decisions regarding the need for special neurological imaging and consultation. It also emphasizes subtle findings that may prevent the erroneous diagnosis of peripheral vertigo in the presence of an acute stroke syndrome.

Errors in weight estimation in the emergency department: comparing performance by providers and patients.

To examine biases in weight estimation by Emergency Department (ED) providers and patients, a convenience sample of ED providers (faculty, residents, interns, nurses, medical students, paramedics) and patients was studied. Providers (n = 33), blinded to study hypothesis and patient data, estimated their own weight as well as the weight of 11-20 patients each. An independent sample of patients (n = 95) was used to assess biases in patients' estimation of their own weight. Data are represented as over, under, or within +/- 5 kg, the dose tolerance standard for thrombolytics. Logistic regression analysis revealed that patients are almost nine times more likely to accurately estimate their own weight than providers; yet 22% of patients were unable to estimate their own weight within 5 kg. Of all providers, paramedics were significantly worse estimators of patient weight than other providers. Providers were no better at guessing their own weight than were patients. Though there was no systematic estimate bias by weight, experience level (except paramedic), or gender for providers, those providers under 30 years of age were significantly better estimators of patient weight than older providers. Although patient gender did not create a bias in provider estimation accuracy, providers were more likely to underestimate women's weights than men's. In conclusion, patient self-estimates of weight are significantly better than estimates by providers. Inaccurate estimates by both groups could potentially contribute to medication dosing errors in the ED.