Northwest Hospital and Medical Center

STUDY DESIGN: Prospective study of 131 patients and volunteers recruited for an analysis of spinal alignment and gravity line (GL) assessment by force plate analysis. OBJECTIVE: To determine relationships between GL, foot position, and spinopelvic landmarks in subjects with varying sagittal alignment. Additionally, the study sought to analyze the role of the pelvis in the maintenance of GL position. SUMMARY OF BACKGROUND DATA: Force plate technology permits analysis of foot position and GL in relation to radiographically obtained landmarks. Previous investigation noted fixed GL-heel relationship across a wide age range despite changes in thoracic kyphosis. The pelvis as balance regulator has not been studied in the setting of sagittal spinal deformity. METHODS: The 131 subjects were grouped by sagittal vertical axis (SVA) offset from the sacrum: sagittal forward (>2.5 cm), neutral (-2.5 cm <or= SVA <or= 2.5 cm), and sagittal backward (SVA <-2.5 cm). Simultaneous spinopelvic radiographs and GL measure were obtained. Offsets between spinopelvic landmarks, heel position, and GL were calculated. Group comparisons were made for all offsets to determine significance. RESULTS: Aside from the offset T9-GL and GL-heels, all other offsets between spinopelvic landmarks and GL revealed significant differences (P < 0.001) across the 3 subject groups. However, with increasing SVA, the GL kept a rather fixed location relative to the feet. A correlation between posterior pelvic shift in relation to the heels with increasing SVA in this study population was confirmed (r = 0.6, P < 0.001). CONCLUSION: Increasing SVA in standing subjects leads to a posterior pelvic shift in relation to the feet. However, no significant difference in GL-heel offset is noted with increasing SVA. It thus appears that pelvic shift (in relation to the feet) is an important component in maintaining a rather fixed GL-Heels offset even in the setting of variable SVA and trunk inclination.

OBJECTIVES: This study examined renin-angiotensin-aldosterone system (RAAS) inhibitor dose levels in a US patient population and investigated the impact of hyperkalemia on RAAS inhibitor dose and the association between dose levels and clinical outcomes. STUDY DESIGN: De-identified medical records from a large database of electronic health records (Humedica) for patients 5 years of age or older with at least 2 serum potassium readings were analyzed (N = 205,108 patients; 1.7 million records). METHODS: Inclusion criteria required 1 RAAS inhibitor prescription and 12 months' data prior to July 1, 2009 (index date). Patients were classified by comorbidities (chronic kidney disease, heart failure, or diabetes) and RAAS inhibitor dose level at index date, as determined by prescription information. Additional analyses examined RAAS inhibitor dose changes following hyperkalemia and the frequency of cardiorenal adverse outcome/mortality or mortality alone by post index dose level. RESULTS: Dose level was similarly distributed irrespective of patient comorbidity status, with RAAS inhibitors prescribed at maximum dose in 19% to 26% of patients and submaximum dose in 58% to 65% of patients; RAAS inhibitors were discontinued in 14% to 16% of patients. RAAS inhibitor dose was down-titrated after 16% to 21% of hyperkalemia events and discontinued after 22% to 27% of hyperkalemia events. Cardiorenal adverse event/mortality and mortality occurred in 34.3% and 11.0% of patients who discontinued RAAS inhibitors, 24.9% and 8.2% of patients on submaximum doses, and 24.9% and 4.1% of patients on maximum doses, respectively. CONCLUSIONS: Relatively few patients were prescribed maximum doses of RAAS inhibitors, and dose and usage declined following hyperkalemia. Patients on submaximum doses or who discontinued RAAS inhibitors had worse outcomes than patients on maximum doses.

BACKGROUND: Mantle cell lymphoma (MCL) is a distinct subtype of B-cell non-Hodgkin's lymphoma. To the authors' knowledge, little is known regarding its incidence patterns and associated factors. The purpose of the current study was to examine the incidence of MCL over a period of 13 years and to identify the factors associated with the incidence patterns. METHODS: Patients diagnosed with MCL between 1992 and 2004 were identified from the Surveillance, Epidemiology, and End Results (SEER) Tumor registries. SEER*Stat statistical software was used for analysis. RESULTS: Of the 87,166 patients diagnosed with non-Hodgkin's lymphoma during the 13-year period between 1992 and 2004, 2459 (2.8%) had confirmed MCL. The overall incidence of MCL (per 100,000) was 0.55, which increased with age: 0.07 in patients aged <50 years, 2.97 in patients aged 70 to 79 years, and 2.78 in those aged > or =80 years. The age-adjusted incidence rate increased from 0.27 of 100,000 in 1992 to 0.69 of 100,000 in 2004, and the annual percent change was 5.87% (P < .05). The median age at diagnosis was 68 years. The incidence of MCL was higher in men (0.84 of 100,000) than in women (0.34 of 100,000) (P < .05), and was higher in Caucasians (0.61 of 100,000) than in African Americans (0.32 of 100,000). Late-stage (III-IV) MCL was diagnosed in 74.6% of patients. There were significant geographic variations noted (P < .05). CONCLUSIONS: The incidence of MCL increased from 1992 to 2004, and was significantly higher in men, in Caucasians, and patients aged > or =50 years. Most patients were diagnosed with late-stage MCL, and there also were considerable geographic variations observed in incidence rate.

RATIONALE: Hypertrophied hearts switch from mainly using fatty acids (FAs) to an increased reliance on glucose for energy production. It has been shown that preserving FA oxidation (FAO) prevents the pathological shift of substrate preference, preserves cardiac function and energetics, and reduces cardiomyocyte hypertrophy during cardiac stresses. However, it remains elusive whether substrate metabolism regulates cardiomyocyte hypertrophy directly or via a secondary effect of improving cardiac energetics. OBJECTIVE: The goal of this study was to determine the mechanisms of how preservation of FAO prevents the hypertrophic growth of cardiomyocytes. METHODS AND RESULTS: We cultured adult rat cardiomyocytes in a medium containing glucose and mixed-chain FAs and induced pathological hypertrophy by phenylephrine. Phenylephrine-induced hypertrophy was associated with increased glucose consumption and higher intracellular aspartate levels, resulting in increased synthesis of nucleotides, RNA, and proteins. These changes could be prevented by increasing FAO via deletion of ACC2 (acetyl-CoA-carboxylase 2) in phenylephrine-stimulated cardiomyocytes and in pressure overload-induced cardiac hypertrophy in vivo. Furthermore, aspartate supplementation was sufficient to reverse the antihypertrophic effect of ACC2 deletion demonstrating a causal role of elevated aspartate level in cardiomyocyte hypertrophy. 15N and 13C stable isotope tracing revealed that glucose but not glutamine contributed to increased biosynthesis of aspartate, which supplied nitrogen for nucleotide synthesis during cardiomyocyte hypertrophy. CONCLUSIONS: Our data show that increased glucose consumption is required to support aspartate synthesis that drives the increase of biomass during cardiac hypertrophy. Preservation of FAO prevents the shift of metabolic flux into the anabolic pathway and maintains catabolic metabolism for energy production, thus preventing cardiac hypertrophy and improving myocardial energetics.

OBJECTIVE: To determine whether medical conditions that can impair sensory, cognitive, or motor function increase the risk of injury due to motor vehicle collision in older drivers. DESIGN: Case-control study. SETTING: Group Health Cooperative of Puget Sound, a large prepaid health plan. PARTICIPANTS: Group Health members age 65 or older who were licensed drivers in 5 counties. Cases were injured while driving during 1987 or 1988. Controls were matched to cases on age, gender, and county of residence but experienced no such injury during the study years. MEASUREMENTS: The outcome was injury requiring medical care due to a police-investigated motor vehicle collision. Risk factors evaluated included selected medical conditions active within the previous 3 years, as determined from the medical record. MAIN RESULTS: Injury risk was 2.6-fold higher in older diabetic drivers (95% CI: 1.4-4.7), especially those treated with insulin (odds ratio [OR] = 5.8, 95% CI: 1.2-28.7) or oral hypoglycemic agents (OR = 3.1, 95% CI: 0.9-11.0), those with diabetes for over 5 years (OR = 3.9, 95% CI: 1.7-8.7), and those with both diabetes and coronary heart disease (OR = 8.0, 95% CI: 1.7-37.7). Increases were also found for older drivers with coronary artery disease (OR = 1.4), depression (OR = 1.7), alcohol abuse (OR = 2.1), or falls (OR = 1.4), but these associations could easily have arisen by chance. CONCLUSIONS: Counseling about driving risks may be warranted for certain elderly diabetic drivers. Further research is needed to determine whether transient hypoglycemia or long-term complications explain these effects.

For trials of back pain therapy and for many clinical purposes, the outcome of greatest interest may be patient functioning. Physical measurements of muscle strength and range of motion are only weakly correlated with actual patient behavior or symptoms, so the behavior and symptoms must be measured directly. Commonly used physician ratings on ordinal scales are often highly subjective and fail to distinguish particular activities which may improve from those which do not. This paper briefly considers the pressures for improving functional status measurement, describes five criteria for assessing and comparing functional questionnaires, and selectively reviews some newer instruments using these criteria. These newer instruments offer standardization of measurement, comprehensiveness, and generally good reproducibility and validity. Unfortunately, little is known about the responsiveness of these measures to small but clinically important changes. There is a need in this field to define the optimal balance between brevity on the one hand and comprehensiveness on the other, to assess and improve instrument responsiveness, and to compare instruments "head-to-head" to allow rational selection for particular applications.

Hearing impairment has been hypothesized as contributing to symptoms of dementia. Data from a longitudinal study were analyzed to determine if auditory status predicted cognitive functional decline in senile dementia of the Alzheimer's type (SDAT). As part of a larger study, 156 consecutive SDAT outpatients had received a comprehensive medical evaluation including baseline screening for hearing impairment with the finger friction test and serial assessment of cognitive function with the Mini-Mental State examination. Age and cognitive function at entry to the study were greater among individuals with impaired hearing (N = 36) than with normal hearing (N = 120). The demographic profiles of the impaired and normal hearing groups were otherwise similar, as was the prevalence of depression. Intervening mortality rates were nearly identical. Decline in cognitive function one year later, however, was nearly twice as great in the impaired hearing group, a statistically significant difference (P less than .05, by one-tailed t test) even when controlled for age and initial cognitive function. These results, which need to be verified with sophisticated audiometric techniques, suggest that hearing impairment may be a prognostic indicator for subsequent cognitive dysfunction in SDAT. They are consistent with the hypothesized relationship between hearing impairment and dementia in SDAT as well as alternative hypotheses discussed in the text.

Brachytherapy is one of the oldest techniques of radiation therapy for prostate cancer. However, its use has been controversial due to mixed results with older implant techniques and the availability of different treatment methods. New methods of brachytherapy based on improved technology and increased understanding of radiobiology hold promise for consistently improved results. This article describe the various methods of prostate brachytherapy and reviews the clinical results for these methods.

In Brief Study Design. Multicenter prospective consecutive clinical series. Objective. Investigate the interaction between the Adult Deformity Classification and treatment patterns, surgical strategies, surgery effectiveness, and complication rates. Summary of Background Data. An Adult Deformity Classification has been established that applies radiographic parameters of disability. Preliminary intraobserver and interobserver analysis reveals excellent reliability of the classification. Outcomes studies have not been reported to date. Methods. A total of 784 adult patients with thoracolumbar or lumbar deformity underwent radiographic evaluation (full-length frontal/sagittal) as well as health assessment: Oswestry Disability Index, Scoliosis Research Society-22, and SF-12. Patients were subdivided by treatment and surgical strategies; 1 year (111 patients) and 2 year (45 patients) follow-up data were analyzed. Interaction between classification, treatment, surgical strategy, health assessment changes, and complications were analyzed. Results. Classification modifiers (lordosis, subluxation, sagittal balance) were found to have significant variation (higher rates) in surgical care as the grade of the modifier increased. Classification differentiated patients by surgical approach and/or technique. Interaction between classification and baseline health assessment impacts both postoperative health scores and complication rates. Conclusion. This investigation appears to offer the first comprehensive analysis of classification, treatment, and outcomes in a large adult deformity patient group. Significant treatment patterns and outcomes are coming to light as is the impact of surgical strategy A total of 784 patients from a multicenter prospective effort were analyzed according to a validated adult deformity classification. Classification modifiers were found to have a significant impact on surgical rates and surgical strategies. Interaction between classification and baseline health assessment impacts both postoperative health scores and complication rates.

Fifty patients with spinal injury above L2 were studied with MRI; forty-two had initial and followup studies permitting correlation of MRI abnormalities with neurologic improvement. Two discrete patterns of MRI abnormality were identified, presumably representing cord hemorrhage and edema respectively. A third pattern appeared to represent a mixed type of injury. The correlation between the MRI patterns of cord injury and neurologic recovery was excellent. The ability of MRI to demonstrate and characterize acute cord injury appears to exceed that of other diagnostic techniques.

BACKGROUND: Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. METHODS: We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm(3), fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. RESULTS: 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. CONCLUSIONS: In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

BACKGROUND: A cardiac catheterization laboratory can be a frightening environment and music can be a supportive source of environmental sound that stimulates and maintains relaxation. AIM: To test the effects of patient focused music versus loudspeaker music versus standard sound on patient's experiences of anxiety and well-being during coronary angiographic procedures. METHODS: A prospective, randomized, controlled trial of 98 subjects undergoing elective coronary angiogram and/or percutaneous coronary intervention. The subjects were randomly allocated to three different groups of sound environments: a control group (the usual sound environment), a patient focused music group (audio pillow) or to a loudspeaker music group. RESULTS: Anxiety decreased significantly and well-being increased significantly in the two music groups compared to the control group. There was a significantly more positive impression of the sound environment in the patient focused music group compared to the two other groups. CONCLUSION: This study showed that the use of a specially designed music reduced anxiety and increased well-being in patients during coronary angiographic procedures. However, patient focused music seemed to be more preferable. The sound environment was rated more positively by the subjects listening to music via audio pillow. The music delivered via loudspeakers seemed to distract the staff during the examination at the cardiac catheterization laboratory.

BACKGROUND: Healthcare workers (HCWs) who serve on the front lines of the coronavirus disease 2019 (COVID-19) pandemic have been at increased risk for infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in some settings. Healthcare-acquired infection has been reported in similar epidemics, but there are limited data on the prevalence of COVID-19 among HCWs and their associated clinical outcomes in the United States. METHODS: We established 2 high-throughput employee testing centers in Seattle, Washington, with drive-through and walk-through options for symptomatic employees in the University of Washington Medicine system and its affiliated organizations. Using data from these testing centers, we report the prevalence of SARS-CoV-2 infection among symptomatic employees and describe the clinical characteristics and outcomes among employees with COVID-19. RESULTS: Between 12 March 2020 and 23 April 2020, 3477 symptomatic employees were tested for COVID-19 at 2 employee testing centers; 185 (5.3%) employees tested positive for COVID-19. The prevalence of SARS-CoV-2 was similar when comparing frontline HCWs (5.2%) with nonfrontline staff (5.5%). Among 174 positive employees reached for follow-up at least 14 days after diagnosis, 6 reported COVID-related hospitalization; all recovered. CONCLUSIONS: During the study period, we observed that the prevalence of positive SARS-CoV-2 tests among symptomatic HCWs was comparable to that of symptomatic nonfrontline staff. Reliable and rapid access to testing for employees is essential to preserve the health, safety, and availability of the healthcare workforce during this pandemic and to facilitate the rapid return of SARS-CoV-2-negative employees to work.

OBJECTIVES: The objective of this study is to determine if exercise increases joint symptoms in older adults with a history of arthritis or produces symptoms in older adults without such history. In addition, we examine whether joint symptoms explain the large observed variation in strength gain in older adults undergoing vigorous strength training exercise, and report the incidence of musculoskeletal injuries upon initiation of an exercise program. DESIGN: A population-based, single blinded, randomized controlled trial with three exercise groups and one control group. SETTING: A large urban health maintenance organization. PARTICIPANTS: Older men and women (N = 105) aged 68 to 85, with leg strength below the 50th percentile for their age, sex, height, and weight and without neuromuscular disease or active cardiovascular disease. INTERVENTIONS: Supervised exercise in 1-hour sessions, three times each week, for 24 to 26 weeks. One exercise group did strength training (ST) using weight machines (n = 25); another group did endurance training (ET) using stationary cycles (n = 25); and the third group did combined strength training and endurance training (ST+ET) (n = 25). The control group (n = 30) received no intervention. MEASUREMENTS: Strength was measured at the ankle, knee, hip, and elbow using an isokinetic dynamometer. Joint symptoms were rated on a 6-point scale (0 = none, 5 = severe). Arthritis severity was based on self-reported use of arthritis medication. Health status was measured with subscales of the SF-36 and Sickness Impact Profile (SIP). RESULTS: Joint symptoms fluctuated over time in all exercise groups, but they did not improve or worsen significantly in any group. The physical dimension of the SIP and SF-36 subscale scores, including Bodily Pain Scores, did not change over time in any group. Subjects with arthritis and joint symptoms gained as much strength with strength training as did subjects without joint symptoms. Adjustment for age, gender, baseline strength, adherence, and exercise group did not affect this finding. The rate of minor musculoskeletal injuries was 2.2 injuries per 1000 exercise hours. CONCLUSIONS: Moderate intensity stationary cycle exercise and vigorous intensity strength training do not appear to produce or exacerbate joint symptoms in older adults. Joint symptoms did not explain the large variation in gains in strength in older adults participating in a standardized strength training exercise program. Musculoskeletal injuries occurred relatively infrequently, and no major injuries occurred. In evaluating joint pain that occurs in older adults in well regulated exercise programs, clinicians should consider other etiologies before attributing pain to exercise per se.

OBJECTIVES: : To determine whether adenosine is useful and safe as a diagnostic and therapeutic agent for patients with undifferentiated wide QRS complex tachycardia. The etiology of sustained monomorphic wide QRS complex tachycardia is often uncertain acutely. DESIGN: : A retrospective observational study. SETTING: : Treatment associated with emergency visits at nine urban hospitals. PATIENTS: : Consecutive patients treated with adenosine for regular wide QRS complex tachycardia between 1991 and 2006. INTERVENTIONS: : Treatment with adenosine infusion. MEASUREMENTS AND MAIN RESULTS: : Measured outcomes included rhythm response to adenosine, if any, and all adverse effects. A positive response was defined as an observed change in rhythm including temporary atrioventricular conduction block or tachycardia termination. A primary adverse event was defined as emergent electrical or medical therapy instituted in response to an adverse adenosine effect. A rhythm diagnosis was made in each case. The characteristics of adenosine administration as a test for a supraventricular as opposed to ventricular tachycardia were determined, and the adverse event rates were calculated. A total of 197 patients were included: 104 (90%) of 116 (95% confidence interval, 83%-95%) and two (2%) of 81 (95% confidence interval, 0.3%-9%) supraventricular tachycardia and ventricular tachycardia patients demonstrated a response to adenosine, respectively. The odds of supraventricular tachycardia increased by a factor of 36 (95% confidence interval, 9-143) after a positive response to adenosine. The odds of ventricular tachycardia increased by a factor of 9 (95% confidence interval, 6-16) when there was no response to adenosine. The rate of primary adverse events for patients with supraventricular tachycardia and ventricular tachycardia was 0 (0%) of 116 (95% confidence interval, 0%-3%) and 0 (0%) of 81 (95% confidence interval, 0%-4%), respectively. CONCLUSIONS: : Adenosine is useful and safe as a diagnostic and therapeutic agent for patients with regular wide QRS complex tachycardia.

BACKGROUND: Depletion of reduced glutathione is associated with PD and glutathione augmentation has been proposed as a disease-modifying strategy. The aim of this study was to determine the safety and tolerability of intranasal reduced glutathione in individuals with PD. METHODS: Thirty individuals with PD were randomized to either placebo (saline), 300 mg/day, or 600 mg/day of intranasal glutathione in three divided daily doses. Follow-up visits included side effect screening of PD symptoms and cognition, blood chemistry, sinus irritation, and hyposmia. Tolerability was measured by frequency and severity of reported adverse events, compliance, and withdrawals from the study. RESULTS: After 3 months, there were no substantial differences between groups in the number of adverse events reported or observed among all safety measures assessed. All groups met tolerability criteria. CONCLUSIONS: These data support the safety and tolerability of intranasal glutathione in this population. Pharmacokinetic and dose-finding studies are warranted.

A fetus, subsequently shown to have the deletion 17p13, was detected at 30 weeks' gestation because of multiple anomalies and polyhydramnios on ultrasonography. The fetus died and was born at 34 weeks of gestation. Pathologic examination showed intrauterine growth retardation, double outlet right ventricle (a conotruncal cardiac defect), and thymic hypoplasia suggesting partial DiGeorge anomaly. To our knowledge, DiGeorge anomaly has not been reported previously in conjunction with del(17p) nor in the Miller-Dieker syndrome. Since this deletion is the largest deletion of distal 17p observed so far, one explanation for this association may be the presence of a gene on proximal 17p for neural crest development.

OBJECTIVES: The specific goals of the study were to compare three health status measures among older adults for their correlations with similar scales and to examine whether extreme (positive) health states might lead to measurement problems. We also report on practical administration and response problems among older adults. DESIGN: Eligible and randomly selected health plan enrollees aged 65 and older were sent a baseline survey about their health. A random sample of persons who returned this survey was recruited to participate in the comparative study. Additional questionnaires were completed by mail and telephone interviews. Measures were repeated at a 1-year follow-up mailing. SETTING: This study was conducted at Group Health Co-operative (GHC) of Puget Sound, a large prepaid health maintenance organization. PARTICIPANTS: Subjects were 200 of the 283 older adults selected (68.2% response). Mean age was 72.5 years. MEASUREMENTS: The primary measures were the Sickness Impact Profile (SIP), the Quality of Well-being Scale (QWB), and three scales of the Medical Outcomes Study Short-Form 36 (SF-36). Also included were a stress scale, the Positive Affect Scale, and the Chronic Disease Score (CDS) computed from the automated pharmacy data. RESULTS: SIP scores showed a very strong skew toward low (good health) scores with a mean of 3.4% (+/- SD 4.4). The QWB scores ranged from .50 to .90 (mean .73 +/- .09). For the MOS SF-36 scales, scores of 100 (good health) were common for both of the physical health scales but not for general health. Analyses showed the SIP, QWB, and MOS SF-36 scales were moderately to strongly correlated with similar measurement scales and with the independent measure of chronic disease and psychosocial health. Scales repeated at 1 year were highly correlated: intraclass correlation coefficients between baseline and 1 year ranged from an r = .51 to .73. CONCLUSIONS: Our results suggest that the SIP is not a useful tool for rating healthy, community-dwelling older adults. Two MOS SF-36 measures used in this study showed some tendency for "ceiling" measurement effects. The QWB demonstrated an acceptable distribution of scale scores; however, it is the most complex of the three measures to administer. Among the broad range of older adults, no one tool appears to apply to every situation.

STUDY OBJECTIVE: This is an attempt to present an analysis of the literature examining objective information concerning the likelihood of medicolegal errors as it applies to current medical practice. Hopefully this information will be synthesized to generate a cogent approach to manage risk in emergency medicine. METHODS: Articles were obtained by an English language search of MEDLINE from January 1976 to July 2003. This computerized search was supplemented with literature from the author's personal medicolegal collection of peer review articles. This information was presented in a qualitative fashion. RESULTS: There was a steady increase in both the incidence and the recovery amount of verdicts involving general malpractice litigation. There are clearly high-risk emergency medicine categories responsible for most malpractice events, involving such commonly encountered conditions such as chest pain, abdominal pain, pediatric fever, central nervous system (CNS) bleeding, and abdominal aortic aneurysm (AAA). Interestingly, there is a second peak of more minor emergencies, specifically wounds with neglected foreign bodies and missed fractures. Clearly, the largest dollar amount recovery still involves chest pain with subsequent missed transmural myocardial infarction (MI). Interestingly, there does not appear to be a strong correlation between adverse events, outcome and medicolegal risk. Likewise, there does not appear to be a strong correlation between socioeconomic status and a propensity to sue, but there were some defined links with physician profiles involving past malpractice history, as well as prior adverse relationships or communication skills to subsequent claims. Interestingly, a significant association appears to be advertising placed by local law offices seeking to provide services. Lastly in the emergency medical services (EMS) realm, the single strongest correlate to malpractice was the likelihood of an ambulance accident and not related to care delivered itself. CONCLUSION: The current emergency medicine medicolegal dilemmas are a complex interaction of both patient and physician factors specifically targeting several disease categories and damage claims. Awareness of these issues can help to minimize subsequent medicolegal risk and improve patient care.

PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataracts) is a recently described autosomal-recessive neurodegenerative disease caused by mutations in the α-β-hydrolase domain-containing 12 gene (ABHD12). Only five homozygous ABHD12 mutations have been reported and the pathogenesis of PHARC remains unclear. We evaluated a woman who manifested short stature as well as the typical features of PHARC. Sequence analysis of ABHD12 revealed a novel heterozygous c.1129A>T (p.Lys377*) mutation. Targeted comparative genomic hybridization detected a 59-kb deletion that encompasses exon 1 of ABHD12 and exons 1-4 of an adjacent gene, GINS1, and includes the promoters of both genes. The heterozygous deletion was also carried by the patient's asymptomatic mother. Quantitative reverse transcription-PCR demonstrated ∼50% decreased expression of ABHD12 RNA in lymphoblastoid cell lines from both individuals. Activity-based protein profiling of serine hydrolases revealed absence of ABHD12 hydrolase activity in the patient and 50% reduction in her mother. This is the first report of compound heterozygosity in PHARC and the first study to describe how a mutation might affect ABHD12 expression and function. The possible involvement of haploinsufficiency for GINS1, a DNA replication complex protein, in the short stature of the patient and her mother requires further studies.