Use of Activated Recombinant Factor VII in Severe Bleeding - Evidence for Efficacy and Safety in Trauma, Postpartum Hemorrhage, Cardiac Surgery, and Gastrointestinal Bleeding.

BACKGROUND: Uncontrolled bleeding continues to be a major cause of mortality in trauma, cardiac surgery, postpartum hemorrhage and liver failure. The aim of this paper is to assess the evidence supporting the efficacy of activated recombinant factor VII (rFVIIa) administration in these settings. METHODS: Electronic literature search. RESULTS: Numerous retrospective trials have mostly shown a decrease in blood transfusion requirements with no increase in thromboembolic events (TEE), but major limitations in trial design make generalization difficult. In most retrospective reports rFVIIa has been administered as a last-ditch attempt to control bleeding, when acidosis, hypothermia and coagulation factor depletion may not allow optimal rFVIIa effect. Prospective randomized controlled trials have not shown any effect of rFVIIa on mortality or TEE, although some have shown a reduction in RBC requirement. CONCLUSION: Stipulated transfusion protocols in prospective trials have reduced anticipated mortality among controls and make future trials for mortality effect unlikely in view of large sample size requirements. Establishment of these protocols and rapid hemostasis are likely to have greater benefits than administration of a single agent.

Age at regular drinking, clinical course, and heritability of alcohol dependence in the San Francisco family study: a gender analysis.

We examined gender differences in age of onset, clinical course, and heritability of alcohol dependence in 2,524 adults participating in the University of California San Francisco (UCSF) family study of alcoholism. Men were significantly more likely than women to have initiated regular drinking during adolescence. Onset of regular drinking was not found to be heritable but was found to be significantly associated with a shorter time to onset of alcohol dependence. A high degree of similarity in the sequence of alcohol-related life events was found between men and women, however, men experienced alcohol dependence symptoms at a younger age and women had a more rapid clinical course. Women were found to have a higher heritability estimate for alcohol dependence (h(2)= .46) than men (h(2)= .32). These findings suggest that environmental factors influencing the initiation of regular drinking rather than genetic factors associated with dependence may in part underlie some of the gender differences seen in the prevalence of alcohol dependence in this population. (Am J Addict 2010;00:1-10).

Heritability of illicit drug use and transition to dependence in Southwest California Indians.

OBJECTIVE: Native Americans have high rates of drug use and dependence yet little is known concerning its etiology or clinical course. These analyses were conducted to describe the heritability of the use of a variety of illicit drugs, as well as the conditional probability of transitioning from use to dependence for each drug class in a community sample of Native American men and women. METHODS: The sample included 460 participants (190 men and 270 women), recruited through community effort, from eight contiguous Indian reservations in Southern California. Participants were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism. The Semi-Structured Assessment for the Genetics of Alcoholism interview retrospectively asks about the initial use and drug dependence of the following illicit drug classes: marijuana, cocaine, stimulants, sedatives, opiates, hallucinogens, and solvents. Heritability of initial use was determined using SOLAR (http://www.sfbr.org/solar/). RESULTS: Ninety-one percent of this select Indian population had tried at least one of the illicit drug classes. The most commonly tried substance was marijuana (88%), followed by stimulants (60%), cocaine (44%), hallucinogens (34%), and solvents (20%). The heritability of initiation of drug use ranged from 0.14 for cocaine to 0.59 for marijuana. The conditional probability of transition from initiation to drug dependence ranged from 0.66 for stimulants to 0.06 for hallucinogens. CONCLUSIONS: These findings suggest that heritability of the initiation of substance use, in Southwest California Indians, may be similar to other population samples. In this population, however, high rates of dependence on marijuana, opiates, and stimulants are seen once initiation of the use of the substance has occurred.

Age of first marijuana use and the occurrence of marijuana use disorders in Southwest California Indians.

In several national surveys a younger age of substance usage has been associated with a higher likelihood of the development of dependence. Some studies have suggested that age at first use is primarily an environmentally driven variable, whereas others suggest that it may be partially mediated by a general vulnerability to exhibit problem behaviors. Although Native Americans, overall, have the highest prevalence of substance dependence of any US ethnic group, the relationship of age of first marijuana use on the development of dependence in Native American populations is relatively unknown. Demographic information and DSM-III-R diagnoses were obtained from 525 Southwest California Indian adults residing on contiguous reservations. Multinomial logistic regression was used to investigate the relationship between age of first use and marijuana use disorders. Early marijuana use was found to be strongly associated with abuse and dependence in this population, even in the presence of several other risk factors including externalizing diagnoses. These data suggest that effective environmental prevention efforts at reducing early marijuana use may be an important strategy to lower the prevalence of use disorders in this high risk population.

P3 components and adolescent binge drinking in Southwest California Indians.

In adolescence, consuming a large number of drinks over a short interval of time (e.g. binging) is not an uncommon occurrence. Since adolescence is an important neurodevelopmental period, the effect of binge drinking on brain and behavior has become a significant health concern. The present study evaluated event-related potentials (ERPs) in young adult Southwest California Indians who had a history of binge drinking during their adolescence. One hundred twenty five participants who were currently 18-25 yrs of age who were free of Axis I psychiatric diagnoses were categorized as: 1) reporting no binge drinking during adolescence (>5 drinks per occasion before age 18) or drug dependence diagnoses 2) reporting binge drinking during adolescence with no drug dependence diagnoses 3) reporting binge drinking during adolescence and drug dependence diagnoses. ERPs were collected using a facial discrimination task. Adolescent alcohol and drug exposure was found to be associated with decreases in the latency of an early P3 component (P350). Decreases in a later component amplitude (P450) were also found in young adults exposed to alcohol, and those exposed to alcohol and drugs. However, that finding appears to be a combined result of predisposing factors such as family history of alcoholism and presence of other externalizing diagnoses. Taken together these preliminary studies suggests that adolescent binge drinking may result in a decreases in P3 component latencies and amplitudes perhaps reflecting a loss or delay in the development of inhibitory brain systems.

Factors associated with remission from cannabis dependence in southwest California Indians.

Cannabis is the most widely used illicit substance in the United States, and rates of cannabis use disorders in some Native American samples have been reported to be higher than in the general U.S. population. However, little is known about factors which are associated with remission from cannabis dependence in any ethnicity. Using the SSAGA, this study examined variables associated with complete remission (defined as no symptoms of dependence for 6 months or more) from DSM-III-R cannabis dependence in 159 Southwest California Indians living on contiguous reservations. Female gender, employment, having more cannabis-induced symptoms, and a shorter duration of dependence were all associated with an increased likelihood of remission. Attention to factors associated with remission from cannabis dependence may be important in designing more effective treatment and intervention programs in this high-risk population.

A co-morbidity of alcohol dependence with other psychiatric disorders in young adult Mexican Americans.

BACKGROUND: Mexican Americans comprise one of the most rapidly growing populations in the U.S. However, information on the co-morbidity of alcohol dependence with other psychiatric disorders in Mexican Americans is sparse. METHODS: Demographic information, DSM-III-R diagnoses, and information differentiating independent from substance-induced anxiety and affective disorders were obtained from 240 Mexican American young adults residing in select areas of San Diego. RESULTS: A high prevalence of alcohol dependence was found in this population. There was significant co-morbidity between alcohol dependence and anxiety, affective, conduct/antisocial, and other substance dependence disorders. Eight percent of the anxiety disorders and 26% of the affective disorders were found to be substance-induced. CONCLUSION: High rates and substantial co-morbidity of alcohol dependence with psychiatric and other substance use disorders were found in this population. These data may be helpful in designing prevention and intervention programs for this high-risk population.

Sleep Quality in an Adult American Indian Community Sample.

STUDY OBJECTIVES: Epidemiological studies have found that insufficient sleep (< 7 h/night) is more common among American Indians/Alaska Natives (AI/AN). In this study we sought to identify specific demographic, clinical, and cultural factors that may be associated with reduced sleep quality in an American Indian community sample. METHODS: Information on demography along with personal medical, psychiatric, and drinking history was obtained using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The adult participants (n = 386, 54% women) had a mean ± standard deviation age of 31.35 ± 14.4 y. Higher degrees of AI ancestry, but not cultural identification, being older than 30 y, and having a high school diploma all were factors predictive of having a short sleep duration (< 6 h). The global score on the PSQI was significantly higher in those participants with a lifetime diagnosis of substance use disorders, anxiety disorders, and affective disorders. Alcohol use disorders and affective disorders were significant predictors of sleep latency whereas anxiety and affective disorders were correlated with waking more often in the night/early morning. Nicotine dependence was associated with having trouble breathing, and alcohol use disorders and anxiety disorders with bad dreams. CONCLUSIONS: Alcohol use disorders are associated with poorer quality of sleep in this population and substance use disorders were associated with different aspects of sleep than anxiety and depressive disorders. These findings add to the understanding of the interactions between sleep and substance use, anxiety, and affective disorders in an understudied and underserved population.

Electrophysiological responses to affective stimuli in American Indians experiencing trauma with and without PTSD.

American Indians are at high risk for exposure to violence and other traumatic events, yet few studies have investigated posttraumatic stress disorder (PTSD) or its neurobiological consequences in Indian communities. In the present study, a sample of American Indians (n = 146) were given a structured diagnostic interview that additionally indexed traumatic life events and symptoms emerging following those events. Electroencephalogram (EEG) spectra and visual event-related potentials (ERPs) to happy, sad, and neutral faces were also recorded from each participant. Ninety-nine percent of the sample had experienced at least one category of trauma with the mean number being 5, 27% had experienced at least 8 categories, and 13% met DSM-IV criteria for PTSD. The PTSD group did not differ on any demographic or diagnostic variables from the larger sample. An electrophysiological signature for PTSD was found that included increases in high-frequency gamma activity (20-40 Hz, F = 8.7, P < 0.004) in frontal leads, higher N1 amplitudes to sad stimuli in frontotemporal leads (F = 12.4, P < 0.001, F = 5.0, P < 0.03), and longer latency P3 components to happy stimuli in midline, central, and right frontal leads (F = 4.7, P < 0.03; F = 4.1, P < 0.04; F = 4.0, P < 0.05). These findings were observed in participants with PTSD, but not in a group with equivalently high trauma counts. These findings suggest that PTSD is associated with EEG hyperarousal, higher attentional levels to sad stimuli, and slower processing of happy stimuli. They also partially confirm ERP data reported in combat victims with PTSD suggesting that PTSD may induce neurobiological consequences that transcend type of eliciting trauma as well as ethnic and cultural factors.

Co-morbidity of select anxiety, affective, and psychotic disorders with cannabis dependence in Southwest California Indians.

Cannabis dependence is co-morbid with psychiatric disorders in general population surveys, but whether co-morbidity exists in American Indian populations is unknown. The aim of this study was to assess co-morbidity between cannabis dependence and psychiatric disorders in a community sample of Southwest California (SWC) Indians. Demographic information and DSMIII- R diagnoses, including differentiation of independent and cannabis-induced psychiatric disorders, were obtained using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) developed for the Collaborative Study on the Genetics of Alcoholism (COGA) from 513 SWC Indian adults residing on contiguous reservations. Although SWC Indians in this sample had high rates of cannabis dependence (43% in men and 24% in women), cannabis-induced psychiatric disorders each occurred in 1% or less of the sample. No significant co-morbidity with independent psychiatric disorders was found. In SWC Indians, cannabis dependence may be less etiologically related to psychiatric disorders than in the general population.

Testing of an orthogonal measure of cultural identification with adult mission Indians.

The Orthogonal Cultural Identification Scale (OCIS; Oetting & Beauvais, 1990-91) has been validated among Native American youth, but not adults. The present study sought to test the reliability (internal consistency) and validity (construct and factorial) of the OCIS among an adult Native American sample consisting of 389 Mission Indians (61% female). Participants were recruited from reservations using a venue sampling strategy. The OCIS was completed as part of a self-assessment packet of questionnaires. Internal consistency for OCIS subscale scores ranged from 0.76 to 0.91. Both concurrent and discriminant validity were demonstrated. Confirmatory factor analysis revealed 2 factors: (1) Anglo American Identification and (2) Native American Identification. These results indicate the OCIS is a reliable and valid instrument for use with adult Native Americans.

Clinical characteristics of alcohol combined with other substance use disorders in an American Indian community sample.

BACKGROUND: Alcohol and other substance use disorders (SUD) pose major problems of morbidity and mortality in some American Indian communities, but little is known about the clinical characteristics, risk factors, and consequences of combined alcohol and other substance use disorders (multi-substance use disorder, MSUD) in those communities. METHODS: Using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), in a community sample of 876 American Indians, the clinical characteristics of lifetime DSM-5 moderate or severe alcohol use disorder alone (AUD alone) (n=146) and MSUD (defined as alcohol and ≥1 other SUD) (n=284) were evaluated and compared to 347 participants with no lifetime SUD (no SUD). RESULTS: The majority (57%) of participants with a SUD had multi-substance use disorder and 94% of those were with AUD. Stimulants (cocaine and/or amphetamine) and/or cannabis were the most common other SUDs. Participants with AUD alone were more likely to be male and have an earlier age of first alcohol intoxication than those with no SUD. Those with MSUD were more likely to have dropped out of high school, have antisocial personality disorder (ASPD) or conduct disorder (CD), have earlier ages of first alcohol intoxication and first use of cannabis and stimulants, an earlier age of onset of AUD, and more of several AUD symptoms than those with AUD alone, but the same temporal course and time to remission of AUD. CONCLUSIONS: MSUD is prevalent in this sample, is associated with multiple comorbidities and denotes a more severe alcohol syndrome than AUD alone.

Item response theory analyses of DSM-IV and DSM-5 stimulant use disorder criteria in an American Indian community sample.

BACKGROUND: Native Americans experience some of the highest rates of DSM-IV stimulant dependence (SD) of all U.S. ethnic groups. This report compares DSM-IV and DSM-5 stimulant use disorder (SUD) diagnostic criteria in an American Indian community sample. METHODS: Demographic information, stimulant (methamphetamine or cocaine) use, and lifetime DSM-IV and DSM-5 diagnoses were assessed in 858 adult American Indians. Item Response Theory (IRT) analyses were used to assess SUD criteria in both DSM-IV and DSM-5 criteria sets along an underlying latent trait severity continuum and the effect of demographic variables on differential item functioning (DIF) in those criteria. RESULTS: The overall rate of DSM-IV SD was 33%, of DSM-IV SUD was 38%, and of DSM-5 SUD was 36% with no gender differences. All SUD symptoms in both the DSM-IV and DSM-5 datasets functioned on the moderate portion of the underlying severity continuum. "Craving" discriminated better than any other criterion at its level of severity in indicating the presence or absence of SUD. There was little DIF in groups defined by gender or any other demographic variable in either the DSM-IV or DSM-5 datasets. CONCLUSIONS: These findings indicate that in this American Indian sample, diagnostic criteria for DSM-IV and DSM-5 SUD function similarly in terms of severity and DIF and that the abolition of the DSM-IV distinction between stimulant abuse and dependence in DSM-5 is warranted.

Stimulant dependence and stimulant-associated psychosis: clinical characteristics and age of onset in a native American community sample.

OBJECTIVES: Native Americans experience some of the highest rates of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) stimulant dependence (SD) of all US ethnic groups. The present report examined the clinical characteristics and age of onset of stimulant use, SD, remission from SD, and stimulant-associated psychosis (SAP) in a Native American community sample. METHODS: Demographic information, stimulant (methamphetamine or cocaine) use, and lifetime Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) psychiatric disorder diagnoses were assessed in 858 Native Americans. Logistic regression was used to assess the associations of demographic, stimulant use, and psychiatric disorder variables with SD, remission from SD, and SAP. Kaplan-Meier survival analyses were used to assess time from first use to the onset of SD. RESULTS: The overall rate of SD was 33%, of remission from SD 73%, and of SAP 17%. Stimulant dependence was associated with older age, less current annual household income, fewer lifetime years of education, intravenous stimulant use, and earlier age of first stimulant use. Remission from SD was associated with older age, currently being married, and never having used stimulants intravenously. Attention-deficit/hyperactivity disorder (assessed as a lifetime disorder), increased number of years of daily stimulant use, and intravenous use were independently associated with SAP. Younger age at first use was significantly associated with shorter survival to the onset of SD. CONCLUSIONS: Stimulant dependence is prevalent in this population and is associated with less income and education and an earlier age at first use. Intravenous stimulant use adds additional risk for SD, nonremission, and psychosis.

Contributions of ethnicity to differential item functioning of cannabis abuse and dependence symptoms.

OBJECTIVE: Cannabis is the most widely used illicit drug in the United States, and as a result, it is associated with significant public health costs. The present study sought to investigate whether item response theory (IRT) methods could be used to identify meaningful differences in how cannabis abuse and dependence symptoms (determined by criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) function as indices of the severity of misuse across two ethnic groups: Native Americans and European Americans. METHOD: Participants were drawn from two previously collected samples, a population of Native Americans living on contiguous reservations (n = 406) and the University of California at San Francisco Family Alcoholism Study (n = 728). Cannabis use disorder symptoms were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism. RESULTS: Exploratory factor analysis demonstrated that the cannabis abuse and dependence symptoms indexed a single latent trait measuring severity of cannabis use. IRT and multiple indicators multiple causes (MIMIC) analyses suggested meaningful differences in the functioning of these symptoms across ethnic groups. Withdrawal represented a more prevalent and less severe symptom among Native Americans relative to European Americans, whereas each of the cannabis abuse symptoms and a symptom assessing psychological and health problems resulting from cannabis use were less prevalent but more severe in Native Americans. CONCLUSIONS: The findings suggest differences in how cannabis use disorders manifest in these populations and thus have implications for the assessment of these disorders as well as theories attempting to explain the increased rates of substance use diagnoses more generally among Native Americans living on reservations.

Cannabis dependence in the San Francisco Family Study: age of onset of use, DSM-IV symptoms, withdrawal, and heritability.

Cannabis is the most widely used illicit drug in the United States, yet the role of genetics in individual symptoms associated with cannabis use disorders has not been evaluated. The purpose of the present set of analyses was to describe the symptomatology and estimate the heritability of DSM-IV criteria/symptoms of cannabis dependence in a large sample of families. Participants were 2524 adults, participating in the University of California San Francisco (UCSF) Family Study of alcoholism. Seventy percent of the sample had ever used cannabis and 13.9% met DSM-IV criteria for cannabis dependence. Younger age at first cannabis use was found to be significantly associated with a shortened survival to becoming cannabis dependent. Although a greater percentage of men met criteria for cannabis dependence, women were found to demonstrate "telescoping" as indexed by a shorter survival time from initial use to dependence as compared to men. A cannabis withdrawal syndrome was identified in users, the primary symptoms of which were nervousness, appetite change, and sleep disturbance. Cannabis use (h(2)=0.31) and dependence (h(2)=0.20), age at first use, individual DSM-IV criteria for dependence, and cannabis-use associated symptoms of depression, trouble concentrating and paranoia were all found to be heritable. These findings suggest that within this population that cannabis use and dependence, as well as individual cannabis dependence symptoms have a significant heritable component, that cannabis dependence is more likely to occur when use begins during adolescence, and that the cannabis dependence syndrome includes a number of heritable untoward psychiatric side effects including withdrawal.

Item response theory analysis of lifetime cannabis-use disorder symptom severity in an American Indian community sample.

OBJECTIVE: The aim of this study was to use Item Response Theory to assess Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R), lifetime cannabis-use disorder (CUD) symptom severity and its relationship to first cannabis use before age 15 years, male gender, and childhood conduct disorder in an American Indian community sample. METHOD: The Semi-Structured Assessment for the Genetics of Alcoholism was used to determine demographic information, age at first use, and DSM-III-R childhood conduct disorder and lifetime CUD symptoms in a community sample of 349 American Indian participants who had used cannabis at least 21 times in a single year. Two-parameter Item Response Theory models generated marginal maximum likelihood estimates for discrimination (a) and threshold (b) parameters for nine DSM-III-R CUD symptoms along an underlying latent CUD severity continuum. Differential Item Functioning (DIF) analysis was used to assess for differences in symptom severity in groups defined by presence versus absence of age at first use before 15 years, male gender, and childhood conduct disorder. RESULTS: CUD symptoms of "use in larger amounts or over longer periods of time," "activities given up," and "role failure" were the most severe symptoms. All CUD symptoms fell on the moderate portion of the severity continuum. "Time spent" was more severe in individuals who first used cannabis after age 15 years, "hazardous use" was more severe in females, and "use in larger amounts or over longer periods of time" was more severe in individuals with co-morbid childhood conduct disorder. CONCLUSIONS: Specific risk factors for the development of lifetime CUD are associated with increased severity of several CUD symptoms in this high-risk group.

Factors associated with remission from alcohol dependence in an American Indian community group.

OBJECTIVE: This study identified factors associated with remission from DSM-III-R alcohol dependence in an American Indian community group. METHOD: Participants were assessed by using the Semi-Structured Assessment for the Genetics of Alcoholism. RESULTS: Five hundred eighty participants were assessed for alcohol use and alcohol use symptoms; 254 participants were found to have alcohol dependence. The rate of remission in this group was 59%. Thirty-four percent of remitters and 39% of nonremitters had received treatment for alcohol problems. Remission from alcohol dependence was associated with being female, older, and married; an earlier age of onset of alcohol dependence; and self-reported depression symptoms from drinking. Absence of remission was associated with continuing to drink despite knowing one had medical problems from drinking and self-reported anxiety symptoms from drinking. CONCLUSIONS: Attention to factors associated with remission from alcohol dependence may be important in designing more effective treatment and prevention programs in this high-risk population.

Age at first intoxication and alcohol use disorders in Southwest California Indians.

BACKGROUND: In several national surveys, a younger age of onset of first drink and/or regular drinking has been associated with a higher likelihood of the development of alcohol dependence. Some studies have suggested that age at first drink is primarily an environmentally driven variable whereas others suggest that it may be partially mediated by a general vulnerability to exhibit problem behaviors. Although Native Americans, overall, have the highest prevalence of alcohol dependence of any U.S. ethnic group, the relationship of age of onset of intoxication with alcohol dependence in Native American populations is relatively unknown. METHODS: Demographic information and DSM-III-R diagnoses were obtained from 525 Southwest California (SWC) Indian adults residing on contiguous reservations. Survival analyses and Cox and logistic regression were used to investigate the relationship between age of onset of first intoxication and the development of alcohol dependence. Heritability of the age of onset of first intoxication was also determined using SOLAR. RESULTS: Age at first intoxication was not found to be heritable in this population. Early onset of intoxication, however, was found to be significantly associated with both a shorter time to onset of alcohol dependence and increased prevalence in this population, even on taking into account several other risk factors including externalizing diagnoses. CONCLUSIONS: These data suggest that effective environmental prevention efforts at reducing underage drinking may be an important strategy to lower the prevalence of alcohol dependence in this high-risk population.