The individual survival benefits of tumor necrosis factor soluble receptor and fluid administration are not additive in a rat sepsis model.

BACKGROUND: Tumor necrosis factor (TNF) antagonists [e.g., TNF soluble receptor (TNFsr)] improved survival in preclinical but not clinical sepsis trials. However fluid support-itself beneficial-is standard clinically but rarely employed in preclinical sepsis models. We hypothesized that these therapies may not have additive benefit. METHODS AND RESULTS: Antibiotic-treated rats (n = 156) were randomized to intratracheal or intravenous Escherichia coli challenges (>LD50) and either placebo or TNFsr and 24 h fluid treatments alone or together. The survival effects of these therapies did not differ significantly comparing challenge routes. When averaged across route, while TNFsr or fluid alone decreased the hazard ratio of death significantly [ln ± standard error (SE): -0.65 ± 0.30 and -0.62 ± 0.30, respectively, p ≤ 0.05], together they did not (p = 0.16). Furthermore, the observed effect of TNFsr and fluid together on reducing the hazard ratio was significantly less than estimated (-0.37 ± 0.29 versus -1.27 ± 0.43, respectively, p = 0.027) based on TNFsr and fluid alone. While each treatment increased central venous pressure at 6 and 24 h, the observed effects of the combination were also less than estimated ones (p ≤ 0.0005). CONCLUSIONS: The individual survival benefits of TNFsr and fluids were not additive in this rat sepsis model. Investigating new sepsis therapies together with conventional ones during preclinical testing may be informative.

Categorizing temporal patterns of arrest in a cohort of adults with serious mental illness.

Temporal patterns of arrest among mental health systems' clientele have not been well explored. This study uses "trajectory analysis," a methodology widely employed by criminologists exploring patterns of desistence in offending, to examine patterns of criminal justice involvement in a cohort of mental health service recipients. Data for this study are from a statewide cohort of individuals who received services from the Massachusetts Department of Mental Health in 1991 (N = 13,876) and whose arrests were followed for roughly 10 years. Zero-inflated Poisson trajectory analysis applied to cohort members having two or more arrests identified five trajectories with widely varying arrest patterns. Analysis of differences in the composition of the five trajectory-based groups revealed few between-group differences in members' demographic and service use characteristics, while certain offense types were disproportionately prevalent among particular trajectory-based groups. The implications of these findings for understanding criminal justice involvement in this population and the utility of the trajectory model for system planning are discussed.

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.

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.

Examining the challenges of recruiting women into a cardiac rehabilitation clinical trial.

PURPOSE: To examine the challenges of recruiting women for a 5-year cardiac rehabilitation randomized clinical trial; the aims of the study were to describe the range of recruitment sources, examine the myriad of factors contributing to ineligibility and nonparticipation of women during protocol screening, and discuss the challenges of enrolling women in the trial. METHODS: The Women's-Only Phase II Cardiac Rehabilitation program used an experimental design with 2 treatment groups. Eligible participants included women who were (1) diagnosed with a myocardial infarction or stable angina or had undergone coronary revascularization within the last 12 months; (2) able to read, write, and speak English; and (3) older than 21 years. Responses to multiple recruitment strategies including automatic hospital referrals, physician office referrals, mass mailings, media advertisements, and community outreach are described. Reasons for ineligibility and nonparticipation in the trial are explored. RESULTS: Automatic hospital order was the largest source of referral (n = 1,367, 81%) accounting for the highest enrollment rate of women (n = 184, 73%). The barriers to enrollment into the cardiac rehabilitation clinical trial included patient-oriented, provider-oriented, and programmatic factors. Of the referral sources, 52% were screened ineligible for provider-oriented reasons, 31% were ineligible due to patient-oriented factors, and 17.4% were linked to the study protocol. Study nonparticipation of those eligible (73.8%) was largely associated with patient-oriented factors (65.2%), with far less due to provider-related factors (4%) or study-related factors (3.4%). CONCLUSION: Standing hospital orders facilitated enrollment to the cardiac rehabilitation clinical trial, yet women failed to participate predominantly due to significant patient-oriented biopsychosocial barriers.

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.

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.

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.

Nitrite reductase activity of hemoglobin as a systemic nitric oxide generator mechanism to detoxify plasma hemoglobin produced during hemolysis.

Hemoglobin (Hb) potently inactivates the nitric oxide (NO) radical via a dioxygenation reaction forming nitrate (NO(3)(-)). This inactivation produces endothelial dysfunction during hemolytic conditions and may contribute to the vascular complications of Hb-based blood substitutes. Hb also functions as a nitrite (NO(2)(-)) reductase, converting nitrite into NO as it deoxygenates. We hypothesized that during intravascular hemolysis, nitrite infusions would limit the vasoconstrictive properties of plasma Hb. In a canine model of low- and high-intensity hypotonic intravascular hemolysis, we characterized hemodynamic responses to nitrite infusions. Hemolysis increased systemic and pulmonary arterial pressures and systemic vascular resistance. Hemolysis also inhibited NO-dependent pulmonary and systemic vasodilation by the NO donor sodium nitroprusside. Compared with nitroprusside, nitrite demonstrated unique effects by not only inhibiting hemolysis-associated vasoconstriction but also by potentiating vasodilation at plasma Hb concentrations of <25 muM. We also observed an interaction between plasma Hb levels and nitrite to augment nitroprusside-induced vasodilation of the pulmonary and systemic circulation. This nitrite reductase activity of Hb in vivo was recapitulated in vitro using a mitochondrial NO sensor system. Nitrite infusions may promote NO generation from Hb while maintaining oxygen delivery; this effect could be harnessed to treat hemolytic conditions and to detoxify Hb-based blood substitutes.

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.

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.

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.

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.

Associations between employees' work schedules and the vocational consequences of workplace injuries.

INTRODUCTION: This study examines the effect of long-hour work schedules and nonstandard shift work (e.g., night and evening shifts) on the ability of injured workers to maintain productive employment following a workplace injury. METHODS: Analyses were based on 13 years of data from the National Longitudinal Survey of Youth. Multivariate logistic regression analyses were performed with one of ten nonstandard schedules as the independent variable and a particular vocational consequences as the dependent variable. Vocational consequences included being unable to perform normal job duties, temporary job reassignment, working less than full time, filing a workers' compensation claim, and quitting or being fired because of the injury. Covariates in the regression model included age, gender, occupation, industry, and region. RESULTS: The most prominent effects of working a nonstandard schedule were a increased risk of being fired (OR = 1.81; 1.15-2.90 CI 95%), quitting (OR = 1.68; 1.20-2.36 CI 95%), or being unable to work full time (OR = 1.33; 1.08-1.64 CI 95%) following an injury, compared to injured workers in conventional schedules. Schedules involving overtime and long working hours generally had a greater impact on vocational consequences following a workplace injury than did schedules involving night, evening, and other nonstandard shift work. CONCLUSIONS: Occupational rehabilitation professionals need to consider the specific type of work schedule when developing effective return-to-work plans for injured workers. Special precautions need to be taken for workers returning to schedules that involve more than 12 h per day, 60 h per week, and long commutes.

A canine model of septic shock: balancing animal welfare and scientific relevance.

A shock canine pneumonia model that permitted relief of discomfort with the use of objective criteria was developed and validated. After intrabronchial Staphylococcus aureus challenge, mechanical ventilation, antibiotics, fluids, vasopressors, sedatives, and analgesics were titrated based on algorithms for 96 h. Increasing S. aureus (1 to 8 x 10(9) colony-forming units/kg) produced decreasing survival rates (P = 0.04). From 4 to 96 h, changes in arterial-alveolar oxygen gradients, mean pulmonary artery pressure, IL-1, serum sodium levels, mechanical ventilation, and vasopressor support were ordered based on survival time [acute nonsurvivors (< or =24 h until death, n = 8) > or = subacute nonsurvivors (>24 to 96 h until death, n = 8) > or = survivors (> or =96 h until death, n = 22) (all P < 0.05)]. In the first 12 h, increases in lactate and renal abnormalities were greatest in acute nonsurvivors (all P < 0.05). Compared with survivors, subacute nonsurvivors had greater rises in cytokines and liver enzymes and greater falls in platelets, white cell counts, pH, and urine output from 24 to 96 h (all P < 0.05). Importantly, these changes were not attributable to dosages of sedation, which decreased in nonsurvivors [survivors vs. nonsurvivors: 5.0 +/- 1.0 vs. 3.8 +/- 0.7 ml x h(-1) x (fentanyl/midazolam/ medetomidine)(-1); P = 0.02]. In this model, the pain control regimen did not mask changes in metabolic function and lung injury or the need for more hemodynamic and pulmonary support related to increasing severity of sepsis. The integration into this model of both specific and supportive titrated therapies routinely used in septic patients may provide a more realistic setting to evaluate therapies for sepsis.

Randomization in clinical trials of titrated therapies: unintended consequences of using fixed treatment protocols.

OBJECTIVE: Clinical trial designs that randomize patients to fixed treatment regimens may disrupt preexisting relationships between illness severity and level of therapy. The practice misalignments created by such designs may have unintended effects on trial results and safety. METHODS: To illustrate this problem, the Transfusion Requirements in Critical Care (TRICC) trial and the Acute Respiratory Distress Syndrome Network low tidal volume (ARMA) trial were analyzed. RESULTS: Publications before TRICC indicated that clinicians used higher transfusion thresholds in patients with ischemic heart disease compared with younger, healthier patients (p = .001). The trial, however, randomized patients (n = 838) to liberal (10 g/dL hemoglobin) or restrictive (7 g/dL) transfusion thresholds. Thirty-day mortality was different and opposite in the liberal compared with the restrictive arm depending on presence (21 vs. 26%) or absence (25 vs. 16%) of ischemic heart disease (p = .03). At baseline in ARMA, consistent with prior publications, physicians set ventilator volumes lower in patients with high airway pressures and poor compliance (8.4-10.6 mL/kg interquartile range) than patients with less severe abnormalities (9.6-12 mL/kg) (p = .0001). In the trial, however, patients (n = 861) were randomized to low (6 mL/kg) or high (12 mL/kg) tidal volumes. In patients with low compliance (<0.6 mL/kg), 28-day mortality was higher when tidal volumes were raised rather than lowered (42 vs. 29%), but this effect was reversed in patients with higher compliance (21 vs. 37%; p = .003). CONCLUSIONS: In TRICC and ARMA, randomization to fixed treatment regimens disrupted preexisting relationships between illness severity and therapy level. This created noncomparable subgroups in both study arms that received care different and opposite from titrated care, that is, practice misalignments. These subgroups reduced the interpretability and safety of each trial. Characterizing current practice, incorporating current practice controls, and using alternative trial designs to minimize practice misalignments should improve trial safety and interpretability.

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.