Defining normal adrenal function testing in the intensive care unit setting: a canine study.

OBJECTIVE: To determine whether intensive care medicine therapies and testing influence hypothalamic-pituitary-adrenal test results. It is routine in intensive care medicine to measure hypothalamic-pituitary-adrenal function, commonly utilizing the adrenocorticotropic hormone stimulation test to diagnose absolute or relative adrenal insufficiency. DESIGN: Prospective, 96-hr animal study. SETTING: Research laboratory. SUBJECTS: Twenty-four healthy canines. INTERVENTIONS: Animals were randomized into two groups--awake and unrestrained or treated with intensive care medicine therapies, including sedation, intubation, and mechanical ventilation. Animals were further randomized to receive dexamethasone (or placebo) or undergo either a total of four or seven adrenocorticotropic hormone stimulation tests over 96 hrs. MEASUREMENTS AND MAIN RESULTS: Sedation, intubation, and mechanical ventilation transiently increased both basal and postadrenocorticotropic hormone total and free cortisol concentrations >2-fold as compared with baseline for the first 24 hrs (p < or = .05 for both). Performance of seven stimulation tests increased both basal and postadrenocorticotropic hormone total and free cortisol concentrations from baseline by >1.5-fold for the duration of the 96-hr study (p < or = .05). Neither sedation, intubation, and mechanical ventilation nor the performance of more stimulation tests affected delta cortisol measurements (total or free cortisol, p = NS). In contrast, dexamethasone suppressed basal total cortisol concentrations by >2-fold (p < or = .005) at all time points and transiently increased delta total cortisol by approximately 35% during the first 24 hrs of the study (p < or = .05). CONCLUSIONS: Total and free cortisol measurements--whether pre- or post- adrenocorticotropic hormone or as a calculated delta--were altered by intensive care therapies or frequent adrenocorticotropic hormone stimulation testing with one exception. Delta free cortisol was the only hypothalamic-pituitary-adrenal measurement unaffected by sedation, intubation, and mechanical ventilation, completion of more adrenocorticotropic hormone stimulation tests, or dexamethasone therapy. These findings support the need to determine normal ranges for hypothalamic-pituitary-adrenal testing in subjects receiving intensive care medicine before establishing laboratory criteria for the diagnosis of relative adrenal insufficiency.

Bundled care for septic shock: an analysis of clinical trials.

CONTEXT: Sepsis bundles have been developed to improve patient outcomes by combining component therapies. Valid bundles require effective components with additive benefits. Proponents encourage evaluation of bundles, both as a whole and based on the performance of each component. OBJECTIVE: Assess the association between outcome and the utilization of component therapies in studies of sepsis bundles. DATA SOURCE: Database searches (January 1980 to July 2008) of PubMed, Embase, and the Cochrane Library, using the terms sepsis, bundles, guidelines, and early goal directed therapy. DATA EXTRACTION: Inclusion required comparison of septic adults who received bundled care vs. nonprotocolized care. Survival and use rates for individual interventions were abstracted. MAIN RESULTS: Eight unblinded trials, one randomized and seven with historical controls, were identified. Sepsis bundles were associated with a consistent (I2 = 0%, p = .87) and significant increase in survival (odds ratio, 1.91; 95% confidence interval, 1.49-2.45; p < .0001). For all studies reporting such data, there were consistent (I2 = 0%, p > or = .64) decreases in time to antibiotics, and increases in the appropriateness of antibiotics (p < or = .0002 for both). In contrast, significant heterogeneity was seen across trials for all other treatments (antibiotic use within a specified time period; administration of fluids, vasopressors, inotropes, and packed red blood cells titrated to hemodynamic goals; corticosteroids and human recombinant activated protein C use) (all I2 > or = 67%, p < .002). Except for antibiotics, sepsis bundle components are still being investigated for efficacy in randomized controlled trials. CONCLUSION: Bundle use was associated with consistent and significant improvement in survival and antibiotic use. Use of other bundle components changed heterogeneously across studies, making their impact on survival uncertain. However, this analysis should be interpreted cautiously as these studies were unblinded, and only one was randomized.

Effects of intra-aortic balloon counterpulsation in a model of septic shock.

BACKGROUND: Fluid refractory septic shock can develop into a hypodynamic cardiovascular state in both children and adults. Despite management of these patients with empirical inotropic therapy (with or without a vasodilator), mortality remains high. OBJECTIVES: The effect of cardiovascular support using intra-aortic balloon counterpulsation was investigated in a hypodynamic, mechanically ventilated canine sepsis model in which cardiovascular and pulmonary support were titrated based on treatment protocols. METHODS: Each week, three animals (n = 33, 10-12 kg) were administered intrabronchial Staphylococcus aureus challenge and then randomized to receive intra-aortic balloon counterpulsation for 68 hrs or no intra-aortic balloon counterpulsation (control). Bacterial doses were increased over the study (4-8 x 10(9) cfu/kg) to assess the effects of intra-aortic balloon counterpulsation during sepsis with increasing risk of death. MAIN RESULTS: Compared with lower bacterial doses (4-7 x 10(9) colony-forming units/kg), control animals challenged with the highest dose (8 x 10(9) colony-forming units/kg) had a greater risk of death (mortality rate 86% vs. 17%), with worse lung injury ([A - a]O2), and renal dysfunction (creatinine). These sicker animals required higher norepinephrine infusion rates to maintain blood pressure (and higher FIO2) and positive end-expiratory pressure levels to maintain oxygenation (p < or = 0.04 for all). In animals receiving the highest bacterial dose, intra-aortic balloon counterpulsation improved survival time (23.4 +/- 10 hrs longer; p = 0.003) and lowered norepinephrine requirements (0.43 +/- 0.17 microg/kg/min; p = 0.002) and systemic vascular resistance index (1.44 +/- 0.57 dynes/s/cm5/kg; p = 0.0001) compared with controls. Despite these beneficial effects, intra-aortic balloon counterpulsation was associated with an increase in blood urea nitrogen (p = 0.002) and creatinine (p = 0.12). In animals receiving lower doses of bacteria, intra-aortic balloon counterpulsation had no significant effects on survival or renal function. CONCLUSIONS: In a canine model of severe septic shock with a low cardiac index, intra-aortic balloon counterpulsation prolongs survival time and lowers vasopressor requirements.

Justice system involvement into young adulthood: comparison of adolescent girls in the public mental health system and in the general population.

We compared arrest onset and frequency and types of charges between a statewide cohort of adolescent girls in the public mental health system and girls of the same age in the general population to investigate important differences that could have policy or intervention implications. Girls in the public mental health system were arrested at earlier ages more frequently and were charged with more serious offenses than were girls in the general population. Our results strongly argue for cooperation between the public mental health and justice systems to provide mental health and offender rehabilitation in their shared population.

Antidepressant adequacy and work status among medicaid enrollees with disabilities: a restriction-based, propensity score-adjusted analysis.

Abstract This cross-sectional study of adult survey respondents with disability and depression (n = 199) enrolled in Massachusetts' Medicaid program examined the association of adequately or inadequately prescribed antidepressant treatment and self-reported work status using conditional logistic regression, controlling for age, gender, race, marital status, education, receipt of SSI/SSDI, self-reported disabling condition, and health status. Confounding by severity was addressed by two methods: restriction of our sample and subsequent stratification by propensity score. Individuals receiving adequate antidepressant treatment had an increased odds of working compared to individuals receiving inadequate treatment, both in analyses in which restriction was used to limit confounding (OR = 3.45, 95% CI = 1.15-10.32, P < .03), and in analyses which combined restriction with adjustment by propensity score stratification (OR = 3.04, 95% CI = 1.01-9.62, P < .05). Among this sample of Medicaid enrollees with disability and depression, those receiving adequate antidepressant treatment were significantly more likely to report working.

Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin.

During intravascular hemolysis in human disease, vasomotor tone and organ perfusion may be impaired by the increased reactivity of cell-free plasma hemoglobin (Hb) with NO. We experimentally produced acute intravascular hemolysis in a canine model in order to test the hypothesis that low levels of decompartmentalized or cell-free plasma Hb will severely reduce NO bioavailability and produce vasomotor instability. Importantly, in this model the total intravascular Hb level is unchanged; only the compartmentalization of Hb within the erythrocyte membrane is disrupted. Using a full-factorial design, we demonstrate that free water-induced intravascular hemolysis produces dose-dependent systemic vasoconstriction and impairs renal function. We find that these physiologic changes are secondary to the stoichiometric oxidation of endogenous NO by cell-free plasma oxyhemoglobin. In this model, 80 ppm of inhaled NO gas oxidized 85-90% of plasma oxyhemoglobin to methemoglobin, thereby inhibiting endogenous NO scavenging by cell-free Hb. As a result, the vasoconstriction caused by acute hemolysis was attenuated and the responsiveness to systemically infused NO donors was restored. These observations confirm that the acute toxicity of intravascular hemolysis occurs secondarily to the accelerated dioxygenation reaction of plasma oxyhemoglobin with endothelium-derived NO to form bioinactive nitrate. These biochemical and physiological studies demonstrate a major role for the intact erythrocyte in NO homeostasis and provide mechanistic support for the existence of a human syndrome of hemolysis-associated NO dysregulation, which may contribute to the vasculopathy of hereditary, acquired, and iatrogenic hemolytic states.

Risk of death does not alter the efficacy of hydrocortisone therapy in a mouse E. coli pneumonia model: risk and corticosteroids in sepsis.

BACKGROUND: Risk of death may influence the efficacy of anti-inflammatory agents in sepsis. "Physiologic" dose corticosteroids, while improving survival in earlier trials with higher control mortality rates (>50%), were not beneficial in the recent CORTICUS trial with lower control mortality (31%). We investigated whether risk of death altered the effects of hydrocortisone in a mouse pneumonia model. METHODS: Mice (n=637) challenged with high, medium or low intratracheal E. coli doses were randomized to receive one of three hydrocortisone doses (5, 25 or 125 mg/kg) or normal saline (NS) only (control) for 4 days. All animals were treated with similar volumes of ceftriaxone and NS support following E. coli and were observed for 168 h. RESULTS: Decreasing E. coli doses reduced control mortality rates (from 94 to 12%). In similar patterns (not significant) each hydrocortisone dose increased the odds ratio (OR) of survival (95% confidence interval) with each E. coli dose (ORs ranging from 1.2 [0.4, 3.7] to 6.1 [0.6, 61.0]). The effect of hydrocortisone on the OR was not related to control mortality rate (r=-0.13, p=0.29) and overall was highly significant (2.04 [1.37, 3.03], p=0.0004). In randomly selected animals 48 h after the highest E. coli dose, compared with the control, hydrocortisone (125 mg/kg) significantly decreased IL-6, INFgamma, and nitric oxide levels. CONCLUSIONS: In this mouse model the beneficial effects of hydrocortisone were independent of risk of death. These findings suggest that factors other than risk of death may underlie the differing effects of corticosteroids in recent sepsis trials.

Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: a meta-analysis.

CONTEXT: Hemoglobin-based blood substitutes (HBBSs) are infusible oxygen-carrying liquids that have long shelf lives, have no need for refrigeration or cross-matching, and are ideal for treating hemorrhagic shock in remote settings. Some trials of HBBSs during the last decade have reported increased risks without clinical benefit. OBJECTIVE: To assess the safety of HBBSs in surgical, stroke, and trauma patients. DATA SOURCES: PubMed, EMBASE, and Cochrane Library searches for articles using hemoglobin and blood substitutes from 1980 through March 25, 2008; reviews of Food and Drug Administration (FDA) advisory committee meeting materials; and Internet searches for company press releases. STUDY SELECTION: Randomized controlled trials including patients aged 19 years and older receiving HBBSs therapeutically. The database searches yielded 70 trials of which 13 met these criteria; in addition, data from 2 other trials were reported in 2 press releases, and additional data were included in 1 relevant FDA review. DATA EXTRACTION: Data on death and myocardial infarction (MI) as outcome variables. RESULTS: Sixteen trials involving 5 different products and 3711 patients in varied patient populations were identified. A test for heterogeneity of the results of these trials was not significant for either mortality or MI (for both, I2 = 0%, P > or = .60), and data were combined using a fixed-effects model. Overall, there was a statistically significant increase in the risk of death (164 deaths in the HBBS-treated groups and 123 deaths in the control groups; relative risk [RR], 1.30; 95% confidence interval [CI], 1.05-1.61) and risk of MI (59 MIs in the HBBS-treated groups and 16 MIs in the control groups; RR, 2.71; 95% CI, 1.67-4.40) with these HBBSs. Subgroup analysis of these trials indicated the increased risk was not restricted to a particular HBBS or clinical indication. CONCLUSION: Based on the available data, use of HBBSs is associated with a significantly increased risk of death and MI.

The relationship of personal assistance service utilization to other Medicaid payments among working-age adults with disabilities.

This study examined changes in Medicaid provider payments prior to and following approval for personal assistance services (PAS) among 471 PAS users compared to 295 nonusers who qualified for but did not use PAS, adjusting for differences between users and nonusers using propensity scores. PAS users showed a significantly greater increase in total monthly payments from pre- to post-PAS approval compared to nonusers (35% vs. -9) due to high average monthly payments for PAS ($1325). However, users showed a decrease in non-PAS payments compared to nonusers (1%-9% vs. -9%), with significant decreases in payments for both acute/rehabilitation hospitalizations and for nursing home/other long-term residential stays among users. While costly, savings in other areas may help reduce the net cost of PAS.

Crime victims and criminal offenders among adults with serious mental illness.

OBJECTIVE: This study compared crime victimization rates with rates of criminal offending among adults with serious mental illness. METHODS: Statistical estimation determined caseload overlap between anonymous extracts from public mental health and criminal justice databases for 13 rural Vermont counties. Participants included 2,610 adults who received community-based services during the study year (July 2005 through June 2006). RESULTS: Among the 2,610 adults 6.6% were identified by police as criminal offenders and 7.1% were identified as crime victims. Compared with the general population, however, their elevated risk of being identified as a victim (2.4) was lower than their elevated risk of being identified as an offender (2.6). These categories are not mutually exclusive. CONCLUSIONS: To better understand involvement in the criminal justice system among adults with serious mental illness, research should consider rates of criminal offending and victimization and compare these with rates for the general population.

Drug-related arrests in a cohort of public mental health service recipients.

OBJECTIVES: The excessive prevalence of comorbid substance abuse among persons with severe mental illness has been well established and identified as the source of numerous negative outcomes. An overlooked aspect of illicit drug use in this population is its illegality and the potentially dire criminal sanctions. This study examined the prevalence of drug arrests in a cohort of persons receiving services from a state mental health agency who were followed for roughly ten years. METHODS: Data on arrest spanning from 1991 to 2000 were obtained for all individuals receiving inpatient, case management, or residential services from July 1991 to June 1992 (N=13,816). Reports of prevalence were based on the number with at least one drug-related arrest in the observation period. RESULTS: Five percent of individuals in the cohort experienced at least one drug-related arrest (N=720). These included simple possession as well as manufacturing and distribution. The prevalence was much higher (15%) among persons aged 18 to 25 years than in other age groups. Roughly 95% of persons with a drug arrest also had an arrest for another type of offense. This pattern is similar to that observed among persons with a drug-related arrest in the general population. CONCLUSIONS: Convictions on drug charges can void access to Section Eight housing and other benefits and are associated with other patterns of offending that also carry significant criminal sanctions. State mental health agencies may wish to target interventions toward youthful clientele by focusing specifically on the risks associated with involvement with illicit drugs.

Arrests of adolescent clients of a public mental health system during adolescence and young adulthood.

OBJECTIVE: This study examined the relationship of age and gender with risk of arrest among adolescents and young adults who were intensive adolescent users of public mental health services. METHODS: Data were obtained from the Massachusetts Department of Mental Health (DMH) and juvenile and criminal courts. Participants were youths receiving DMH adolescent case management services sometime in 1994-1996 who were born between 1976 and 1979 (781 males and 738 females). They were cross-matched to document arrests between age seven and 25. The study examined age at first arrest, age-specific risk, and the relationship between arrest history and arrest risk by gender and age. RESULTS: Most males (69%) and almost half the females (46%) were arrested by age 25. First arrest was most common before age 18. As in the general population, males' arrest patterns were more concerning than those of females, although patterns were of concern in both groups. Most female arrestees had multiple arrests, many as adults. No gender differences were observed for several factors, including risk of first arrest over age 18. Risk was far greater for those arrested in the previous year than for those never arrested. CONCLUSIONS: Findings justify concerns of public mental health systems regarding justice system involvement of adolescent clients. Risk of first arrest was significant from early adolescence through age 24, indicating a need for arrest prevention into young adulthood. The heightened arrest risk at all ages among those who were recently arrested demarcates a population in need of immediate intervention.

DTPA Fe(III) decreases cytokines and hypotension but worsens survival with Escherichia coli sepsis in rats.

OBJECTIVE: Nonselective inhibition of nitric oxide (NO) with NO synthase antagonists decreases hypotension but worsens outcome clinically. We investigated whether iron (III) complex of diethylenetriaminepentaacetic acid [DTPA Fe(III)], a scavenger of NO as well as other oxidant mediators, has similar divergent effects in E. coli challenged rats. METHODS: Animals with venous and arterial catheters and challenged with intrabronchial or intravenous E. coli were randomized to treatment with DTPA Fe(III) in doses from 3 to 800 mg/kg or placebo. Mean blood pressure (MBP) was measured in all animals and plasma NO, cytokines, and blood and lung leukocyte and bacteria counts in animals administered intrabronchial E. coli and DTPA Fe(III) 50 mg/kg or placebo. Animals received antibiotics and were observed 168 h. RESULTS: Independent of drug regimen or infection site, compared to placebo, DTPA Fe(III) increased MBP although this was greater with high vs. lower doses. Despite increased MBP, DTPA Fe(III) worsened the hazards ratio of survival . At 6 and 24 h DTPA Fe(III) decreased NO but not significantly and decreased four cytokines (tumor necrosis factor-alpha, interleukins 1 and 10, and macrophage inflammatory protein 3alpha) and lung lavage neutrophils. From 6 to 24 h DTPA Fe(III) increased blood bacteria. CONCLUSIONS: DTPA Fe(III) while increasing blood pressure has the potential to worsen outcome in sepsis. Further preclinical testing is required before this agent is applied clinically.

Nonstandard shift schedules and the risk of job-related injuries.

OBJECTIVES: This study assessed the extent to which working various types of nonstandard shift schedules (eg, night and evening shifts) is associated with the risk of occupational injuries or illnesses. METHODS: Multivariate analyses were conducted using data from 13 years (1987 to 2000) of the National Longitudinal Survey of Youth (NLSY) encompassing 110 236 job records and over 82 000 person-years of work experience. Cox proportional hazard regression techniques were used to derive hazard ratios comparing the relative risk of suffering a work-related injury among people working night, evening, rotating, split, and irregular shifts to the risks for those working conventional day shifts, after adjustment for age, gender, occupation, industry, and region. Incidence rates were normalized using a common denominator of 100 person-years of "at-risk time" to obtain valid comparisons. RESULTS: All of the nonstandard shift schedules, except split shifts, were found to have a higher risk for occupational injuries and illnesses than conventional day shifts. After control for the selected covariates, the calculated hazard ratios were 1.43 for evening shifts [95% confidence interval (95% CI) 1.26-1.62], 1.36 for rotating shifts (95% CI 1.17-1.58), 1.30 for night shifts (95% CI 1.12-1.52), 1.15 for irregular shifts (1.03-1.30), and 1.06 for split shifts (0.71-1.58). CONCLUSIONS: These findings suggest that nonstandard shifts are not more risky merely because of the concentration of hazardous jobs in those types of schedules or because of underlying differences in the characteristics of employees working nonstandard shifts. The results point to the need to extend targeted injury prevention programs not only to people working night shifts, but also to those who work evenings.

Elevated cancer incidence among adults with serious mental illness.

OBJECTIVE: Research is increasingly focusing on the health status of adults with serious mental illness. This study examined databases in Vermont to determine the incidence of cancer in this population. METHODS: Probabilistic statistical methods were used to determine the overlap between the Vermont Cancer Registry and Vermont mental health treatment databases. RESULTS: The incidence of cancer for adults with mental illness was 1.6 percent, more than twice (2.5 times) that of the general population. Among persons with mental illness, elevated risk was greatest for men younger than 50 years (6.6 times the risk of a comparable group in the general population) and lowest for women aged 50 years and older (1.8 times the risk of a comparable group). CONCLUSIONS: These findings raise important questions about the relationship between serious mental illness and cancer. Future research should consider the effect of lifestyle factors, and potential effects of first- and second-generation antipsychotics should be investigated.

Patterns and prevalence of arrest in a statewide cohort of mental health care consumers.

OBJECTIVE: Although criminal justice involvement among persons with severe mental illness is a much discussed topic, few large-scale studies systematically describe the patterns and prevalence of arrest in this population. This study examined rates, patterns, offenses, and sociodemographic correlates of arrest in a large cohort of mental health service recipients. METHODS: The arrest records of 13,816 individuals receiving services from the Massachusetts Department of Mental Health from 1991 to 1992 were examined over roughly a ten-year period. Bivariate relationships between sociodemographic factors and arrest were also examined. RESULTS: About 28 percent of the cohort experienced at least one arrest. The most common charges were crimes against public order followed by serious violent offenses and minor property crime. The number of arrests per individual ranged from one to 71. Five percent of arrestees (roughly 1.5 percent of the cohort) accounted for roughly 17 percent of arrests. The proportion of men arrested was double that of women. Persons 18 to 25 years of age had a 50 percent chance of at least one arrest. This rate declined with age but did so unevenly across offense types. CONCLUSIONS: The likelihood of arrest appeared substantial among persons with severe mental illness, but the bulk of offending appeared concentrated in a small group of persons and among persons with sociodemographic features similar to those of offenders in the general population. Data such as these could provide a platform for designing jail diversion and other services to reduce both initial and repeat offending among persons with serious mental illness.

An assessment of the extent of child maltreatment using administrative databases.

This study examined the extent of violence toward children and factors associated with child maltreatment in Florida using a cohort of children (N=499,330) who were adjudged to be victims of maltreatment between July 1, 1996, and June 30, 2003. To assess the extent of maltreatment, five indicators were proposed and examined. Multivariate analyses found that prior referral, having more than one type of maltreatment during an initial incident, and caregiver absence best predicted the recurrence of maltreatment. Caregivers' alcohol and substance use were strong predictors of neglect and threatened harm but not of abuse. Finally, multilevel analyses found that older, nonminority girls with histories of prior referrals were significantly (psuedo-zs>2.00) more likely to experience high degrees of incident severity. Caregivers' substance use, excluding alcohol, also was significantly linked to incident severity. Implications of the findings are discussed.

Prophylactic high-dose N(omega)-monomethyl-L-arginine prevents the late cardiac dysfunction associated with lethal tumor necrosis factor-alpha challenge in dogs.

We investigated nitric oxide (NO) as a possible cause of the cardiac dysfunction associated with high, lethal doses of tumor necrosis factor-alpha (TNF-alpha) in dogs. Eighty-seven awake, 2-year-old (10-12 kg), purpose-bred beagles were randomized to receive an infusion of saline or N-monomethyl-L-arginine (L-NMMA), a nonselective NO synthase (NOS) inhibitor, as a 40 mg kg bolus followed by a 40 mg kg(-1) h(-1) infusion for 3 to 6 h 3 h before (prophylactic) or 3 h after (therapeutic) challenge with TNF-alpha (60 microg kg(-1)) or vehicle. Serial radionuclide-heart scans and thermodilution pulmonary artery catheter hemodynamic measurements were performed. The effects of prophylactic L-NMMA on TNF-alpha-induced cardiac dysfunction as measured by decreases in mean left ventricular (LV) ejection fraction and downward and rightward shifts of LV function plots (peak systolic pressure versus end systolic volume index and LV stroke work index versus end diastolic volume index) were significantly different comparing early (3-6 h) and delayed (24 h) time points (P = 0.02). Prophylactic L-NMMA therapy did not appear to fully prevent early (3-6 h) TNF-alpha-induced cardiac dysfunction, but at 24 h, complete protection was seen. Therapeutic L-NMMA did not appear to fully protect the heart from TNF-alpha-induced early or delayed cardiac dysfunction (P = NS). Similarly, L-NMMA given prophylactically, but not therapeutically, blocked TNF-alpha-induced increases in exhaled NO flow rates and plasma nitrite and nitrate concentrations (both P = 0.02). These data suggest that TNF-alpha initiates two phases of cardiac injury: an early (3-6 h) phase that may be partially NO independent and a delayed (24 h) phase that is NO dependent. The delayed, more persistent dysfunction can be completely blocked by high doses of a nonselective NOS inhibitor administered before TNF-alpha.

Neutrophil inhibition with L-selectin-directed MAb improves or worsens survival dependent on the route but not severity of infection in a rat sepsis model.

Both route and severity of infection may influence immunomodulator agents in sepsis. We studied the effect of each variable on HRL-3, an L-selectin-directed MAb that inhibits neutrophil function, in a rat sepsis model. Animals (n = 800) were randomized to be treated with either HRL-3 or placebo and to receive Escherichia coli either intravenously (IV) or intrabronchially (IB) in doses producing low or high mortality rates. Animals received antibiotics and were observed for 168 h. Route but not dose of E. coli altered the effects HRL-3 on mortality rate (mean hazards ratio +/- SE). With IV E. coli, compared with control, HRL-3 was beneficial and reduced the hazards ratio both early (0 to 6 h; -0.75 +/- 0.23) and late (6 to 168 h; -0.72 +/- 0.36) (P = 0.001 and 0.04, respectively, over all E. coli doses). In contrast, with IB E. coli HRL-3 reduced the hazards ratio early (-1.1 +/- 0.36) but worsened it late (0.87 +/- 0.23) (P = 0.002 for both effects over all E. coli doses) in patterns significantly different from IV E. coli (P < 0.0001). Compared with control, although HRL-3 did not alter lung neutrophil numbers or injury score at 6 or 168 h with IV E. coli (P = ns for all), it reduced both early and increased them late with IB E. coli (P

Involvement in the criminal justice system among recipients of mental health services after September 11.

OBJECTIVE: This study examined the relative risk of arrest among recipients of mental health services in Washington, D.C., during the 23 months before and the 13 months after the terrorist attacks of September 11, 2001, with the purpose of identifying any change in involvement with the criminal justice system after the attacks. METHODS: Analysis of anonymous data sets provided by the local mental health and police departments provided measures of risk of arrest, relative to that of the general population, for the approximately 5,000 people receiving mental health services each month. Interrupted time-series analysis was used to measure change in relative risk during the 36-month study period. RESULTS: Significant increases were noted in relative risk of arrest after September 11, 2001, among male, nonwhite young-adult recipients of mental health services. Significant change was evident for eight of the 12 age, gender, and racial groups used in this analysis. CONCLUSIONS: Disaster planning and response should include attention to involvement with the criminal justice system among recipients of mental health services. Future research should focus on the nature of the relationship between terrorism and arrest among service recipients.