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Objective: People hospitalized for depression are often discharged before the acute phase of their illness has resolved and need timely care transitions to prevent relapse. We examined 30-day postdischarge service use for Ontarians, aged 15 years or older, who were hospitalized for depression. We focused on a pattern consistent with guideline and policy directions: higher rates of physician visits, postdischarge, combined with lower rates of emergency department (ED) admissions or rehospitalization.Methods: Administrative data for the fiscal year of 2005 were used to identify hospitalizations for depression and subsequent physician visits, ED admissions, or readmissions for depression within 30 days, postdischarge. Sex, age, income, and geographic location were examined along with the relation between health care resources (beds, EDs, and physicians) and postdischarge service use.Results: Sixty-three percent of patients discharged for depression were followed, within 30 days, by a physician visit for depression. Twenty-five percent were either rehospitalized or visited an ED. Women and people from urban or high income areas were more likely to have postdischarge physician visits. Readmissions and ED visits were correlated with number of EDs, but postdischarge physician visits were not related to the number of general practitioners, family physicians, and psychiatrists in the local area.Conclusion: One-third of Ontarians hospitalized for depression did not receive recommended follow-up outpatient care within 30 days of discharge and one-quarter received follow-up through ED visits or readmissions, highlighting the need to improve coordination and integration across care settings for these patients. There are tested transitional and outpatient models that improve quality and outcomes of depression care that merit serious consideration. [ABSTRACT FROM AUTHOR]

Objective: Gender disparities in mental health highlight the need to include gender equity measures when planning, implementing, and evaluating mental health programs at national, state or provincial, and municipal levels. This study aimed to identify, select, and assess the feasibility of comparing gender-sensitive mental health indicators in a low- (Peru), middle- (Colombia), and high- (Canada) income country.Methods: The indicators were selected by a multidisciplinary group of experts who used criteria and a framework proposed by the World Health Organization. Data from national, population-based databases from each country were used to measure the indicators.Results: Seven indicators (12-month prevalence of the following: depression, psychological distress, generalized anxiety disorder, suicide attempts, alcohol dependence, mental health service use, and psychological impairment) were feasible for measurement in at least two countries. Only five indicators were comparable between two countries, and only one was comparable among all countries (suicide attempts). The indicators that showed the greatest inequities between men and women were depression, anxiety, suicide attempts, use of mental health services, and alcohol dependence. Female-to-male ratios for prevalence of mental illness ranged from .1 to 2.3, and ratios for service use ranged from 1.3 to 1.9. Significant trends were found when the indicators were considered by age, education, marital status, and income.Conclusions: Some of these indicators can be used to identify populations most vulnerable to gender inequities in mental health. The results from this study may provide useful information to program planners who aim to implement, improve, and monitor national mental health strategies that reduce gender inequities under different national conditions. [ABSTRACT FROM AUTHOR]

Rationale: Little is known about the long-term outcomes and costs of survivors of acute respiratory distress syndrome (ARDS).Objectives: To describe functional and quality of life outcomes, health care use, and costs of survivors of ARDS 2 yr after intensive care unit (ICU) discharge.Methods: We recruited a cohort of ARDS survivors from four academic tertiary care ICUs in Toronto, Canada, and prospectively monitored them from ICU admission to 2 yr after ICU discharge.Measurements: Clinical and functional outcomes, health care use, and direct medical costs.Results: Eighty-five percent of patients with ARDS discharged from the ICU survived to 2 yr; overall 2-yr mortality was 49%. At 2 yr, survivors continued to have exercise limitation although 65% had returned to work. There was no statistically significant improvement in health-related quality of life as measured by Short-Form General Health Survey between 1 and 2 yr, although there was a trend toward better physical role at 2 yr (p = 0.0586). Apart from emotional role and mental health, all other domains remained below that of the normal population. From ICU admission to 2 yr after ICU discharge, the largest portion of health care costs for a survivor of ARDS was the initial hospital stay, with ICU costs accounting for 76% of these costs. After the initial hospital stay, health care costs were related to hospital readmissions and inpatient rehabilitation.Conclusions: Survivors of ARDS continued to have functional impairment and compromised health-related quality of life 2 yr after discharge from the ICU. Health care use and costs after the initial hospitalization were driven by hospital readmissions and inpatient rehabilitation. [ABSTRACT FROM AUTHOR]

Background: As more patients survive the acute respiratory distress syndrome, an understanding of the long-term outcomes of this condition is needed.Methods: We evaluated 109 survivors of the acute respiratory distress syndrome 3, 6, and 12 months after discharge from the intensive care unit. At each visit, patients were interviewed and underwent a physical examination, pulmonary-function testing, a six-minute-walk test, and a quality-of-life evaluation.Results: Patients who survived the acute respiratory distress syndrome were young (median age, 45 years) and severely ill (median Acute Physiology, Age, and Chronic Health Evaluation score, 23) and had a long stay in the intensive care unit (median, 25 days). Patients had lost 18 percent of their base-line body weight by the time they were discharged from the intensive care unit and stated that muscle weakness and fatigue were the reasons for their functional limitation. Lung volume and spirometric measurements were normal by 6 months, but carbon monoxide diffusion capacity remained low throughout the 12-month follow-up. No patients required supplemental oxygen at 12 months, but 6 percent of patients had arterial oxygen saturation values below 88 percent during exercise. The median score for the physical role domain of the Medical Outcomes Study 36-item Short-Form General Health Survey (a health-related quality-of-life measure) increased from 0 at 3 months to 25 at 12 months (score in the normal population, 84). The distance walked in six minutes increased from a median of 281 m at 3 months to 422 m at 12 months; all values were lower than predicted. The absence of systemic corticosteroid treatment, the absence of illness acquired during the intensive care unit stay, and rapid resolution of lung injury and multiorgan dysfunction were associated with better functional status during the one-year follow-up.Conclusions: Survivors of the acute respiratory distress syndrome have persistent functional disability one year after discharge from the intensive care unit. Most patients have extrapulmonary conditions, with muscle wasting and weakness being most prominent. [ABSTRACT FROM AUTHOR]

Background: People who have experienced intimate partner violence (IPV) or child maltreatment (CM) are at risk of having lower resilience and adverse psychological outcomes. In keeping with the social and environmental factors that support resilience, there is a need to take a public health approach to its investigation and to identify existing initiatives in particular settings and populations that can guide its deliberate promotion., Method: This narrative synthesis examines quantitative and qualitative studies of interventions with resilience-related outcomes in specified health and other settings. Clinical RCTs are excluded as beyond the scope of this review., Results: Twenty studies were identified for review in several settings, consisting of 14 quantitative studies, 2 review studies, 2 qualitative studies and 2 mixed-methods studies. Three quantitative studies produced strong evidence to support: a home visitation program for at-risk mothers; a methadone program for women and a substance abuse program. This review reveals that few studies use specific resilience measures., Conclusions: The topic has been little studied despite high needs for public health interventions in countries of all types. Interventions and research studies that use specific resilience measures are likely to help measure and integrate what is currently a disparate area., Implications: The participation of people with IPV or CM history in program and research design and implementation is indicated to support advocacy, innovation and sustainable interventions. This is especially pertinent for interventions in LAMIC and indigenous settings where continuing programs are sorely needed., (© The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To compare methodological characteristics of randomized controlled trials (RCTs) published in higher vs. lower impact Core Clinical Journals., Study Design and Setting: We searched MEDLINE for RCTs published in 2007 in Core Clinical Journals. We randomly sampled 1,140 study reports in a 1:1 ratio in higher (five general medicine journals with the highest total citations in 2007) and lower impact journals., Results: Four hundred sixty-nine RCTs proved eligible: 219 in higher and 250 in lower impact journals. RCTs in higher vs. lower impact journals had larger sample sizes (median, 285 vs. 39), were more likely to receive industry funding (53% vs. 28%), declare concealment of allocation (66% vs. 36%), declare blinding of health care providers (53% vs. 41%) and outcome adjudicators (72% vs. 54%), report a patient-important primary outcome (69% vs. 50%), report subgroup analyses (64% vs. 26%), prespecify subgroup hypotheses (42% vs. 20%), and report a test for interaction (54% vs. 27%); P < 0.05 for all differences., Conclusion: RCTs published in higher impact journals were more likely to report methodological safeguards against bias and patient-important outcomes than those published in lower impact journals. However, sufficient limitations remain such that publication in a higher impact journal does not ensure low risk of bias., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Converging lines of evidence suggest that the glutamatergic system may play an increasingly important role in the development of novel therapeutics for major depressive disorder (MDD), particularly agents associated with rapid antidepressant effects. Diverse glutamatergic modulators targeting N-methyl-D-aspartate receptors have shown efficacy in MDD, but their associated psychotomimetic effects presently preclude their use in larger samples. This small, randomized, double-blind, placebo-controlled, crossover pilot study evaluated the potential antidepressant efficacy and tolerability of an oral formulation of the selective N-methyl-D-aspartate NR2B antagonist MK-0657 in patients with treatment-resistant MDD (TRD). The TRD subjects underwent a 1-week drug-free period and were subsequently randomized to receive either MK-0657 monotherapy (4-8 mg/d) or placebo for 12 days. Because of recruitment challenges and the discontinuation of the compound's development by the manufacturer, only 5 of the planned 21 patients completed both periods of the crossover administration of MK-0657 and placebo. Significant antidepressant effects were observed as early as day 5 in patients receiving MK-0657 compared with those receiving placebo, as assessed by the Hamilton Depression Rating Scale and Beck Depression Inventory; however, no improvement was noted when symptoms were assessed with the Montgomery-Asberg Depression Rating Scale, the primary efficacy measure. No serious or dissociative adverse effects were observed in patients receiving this oral formulation of MK-0657. Despite the small sample size, this pilot study suggests that an oral formulation of the NR2B antagonist MK-0657 may have antidepressant properties in TRD patients. Further studies with larger sample sizes are necessary to confirm these preliminary findings.

Background: Survivors of ARDS report depressive symptoms and memory complaints, the prevalence of which after 5 years is unknown., Methods: We administered instruments assessing symptoms of depression (Beck Depression Inventory II [BDI-II]) and memory complaints (Memory Assessment Clinics Self-Rating Scale [MAC-S]) to 64 survivors of ARDS from four university-affiliated ICUs 5 years after ICU discharge. We compared BDI-II scores to quality of life (Medical Outcomes Study 36-Item Short Form [SF-36]) mental health domains (role emotional, mental health, mental component summary), compared BDI-II and MAC-S scores to earlier scores (median, 22 months postdischarge), and examined return to work., Results: Forty-three (67.2%), 46 (71.9%), and 38 (59.4%) patients fully completed the BDI-II, MAC-S ability subscale, and MAC-S frequency of occurrence subscale, respectively. Responders were young (median, 48 years; first-third quartile [Q1-Q3], 39-61 years) with high illness severity. The median BDI-II score was 10 (Q1-Q3, 3-18); eight of 43 (18.6%) had moderate to severe depressive symptoms compared with 14 of 43 (32.6%) earlier (P = .15, n = 38 with paired data). Median MAC-S ability and MAC-S frequency scores were 81 (Q1-Q3, 57-92) and 91.5 (Q1-Q3, 76-105), respectively, similar to earlier scores (P = .67 and P = .64, respectively); 0% to 4.3% scored > 2 SDs below population norms. Higher BDI-II score was predicted by higher earlier BDI-II score, slower recovery of organ function, and longer duration of mechanical ventilation and ICU stay. Higher MAC-S score was predicted by higher earlier MAC-S score. SF-36 mental health domain scores were very stable (P = .57-.83). BDI-II and SF-36 mental health domains were negatively correlated (Spearman coefficient, -0.50 to -0.82). Most patients returned to work regardless of depressive symptoms (minimal to mild, 31 of 35 [88.6%]; moderate to severe, five of eight [62.5%]; P = .12)., Conclusions: Compared with ∼ 2 years postdischarge from the ICU, depressive symptoms and memory complaints were similar at 5 years. Mental health domains of the SF-36 may not be sensitive to small changes in mood symptoms.

Objective: While everyone-including front-line clinicians-should strive to prevent the maltreatment and other severe stresses experienced by many children and adults in everyday life, psychiatrists and other health professionals also need to consider how best to support, throughout the lifespan, those people affected by severe adversity. The first step in achieving this is a clear understanding of the definitions and concepts in the rapidly growing study of resilience. Our paper reviews the definitions of resilience and the range of factors understood as contributing to it, and considers some of the implications for clinical care and public health., Method: This narrative review took a major Canadian report published in 2006 as its starting point. The databases, MEDLINE and PsycINFO, were searched for new relevant citations from 2006 up to July 2010 to identify key papers considering the definitions of resilience and related concepts., Results: Definitions have evolved over time but fundamentally resilience is understood as referring to positive adaptation, or the ability to maintain or regain mental health, despite experiencing adversity. The personal, biological, and environmental or systemic sources of resilience and their interaction are considered. An interactive model of resilience illustrates the factors that enhance or reduce homeostasis or resilience., Conclusions: The 2 key concepts for clinical and public health work are: the dynamic nature of resilience throughout the lifespan; and the interaction of resilience in different ways with major domains of life function, including intimate relationships and attachments.

Background: There have been few detailed, in-person interviews and examinations to obtain follow-up data on 5-year outcomes among survivors of the acute respiratory distress syndrome (ARDS)., Methods: We evaluated 109 survivors of ARDS at 3, 6, and 12 months and at 2, 3, 4, and 5 years after discharge from the intensive care unit. At each visit, patients were interviewed and examined; underwent pulmonary-function tests, the 6-minute walk test, resting and exercise oximetry, chest imaging, and a quality-of-life evaluation; and reported their use of health care services., Results: At 5 years, the median 6-minute walk distance was 436 m (76% of predicted distance) and the Physical Component Score on the Medical Outcomes Study 36-Item Short-Form Health Survey was 41 (mean norm score matched for age and sex, 50). With respect to this score, younger patients had a greater rate of recovery than older patients, but neither group returned to normal predicted levels of physical function at 5 years. Pulmonary function was normal to near-normal. A constellation of other physical and psychological problems developed or persisted in patients and family caregivers for up to 5 years. Patients with more coexisting illnesses incurred greater 5-year costs., Conclusions: Exercise limitation, physical and psychological sequelae, decreased physical quality of life, and increased costs and use of health care services are important legacies of severe lung injury.

Background: As gender is known to be a major determinant of health, monitoring gender equity in health systems remains a vital public health priority. Focusing on a low-income (Peru), middle-income (Colombia), and high-income (Canada) country in the Americas, this study aimed to (1) identify and select gender-sensitive health indicators and (2) assess the feasibility of measuring and comparing gender-sensitive health indicators among countries., Methods: Gender-sensitive health indicators were selected by a multidisciplinary group of experts from each country. The most recent gender-sensitive health measures corresponding to selected indicators were identified through electronic databases (CINAHL, PsycINFO, MEDLINE, Embase, LILACS, LIPECS, Latindex, and BIREME) and expert consultation. Data from population-based studies were analyzed when indicator information was unavailable from reports., Results: Twelve of the 17 selected gender-sensitive health indicators were feasible to measure in at least two countries, and 9 of these were comparable among all countries. Indicators that were available were not stratified or adjusted by age, education, marital status, or wealth. The largest between-country difference was maternal mortality, and the largest gender inequity was mortality from homicides., Conclusions: This study shows that gender inequities in health exist in all countries, regardless of income level. Economic development seemed to confer advantages in the availability of such indicators; however, this finding was not consistent and needs to be further explored. Future initiatives should include identifying health system factors and risk factors associated with disparities as well as assessing the cost-effectiveness of including the routine monitoring of gender inequities in health.

Objective: Knowledge is lacking on the extent to which area-level characteristics contribute to variations observed in the use of mental health services. This study examined the influence of area- and individual-level characteristics on the use of mental health services., Methods: Data from a nationally representative, population-based, cross-sectional survey, the Canadian Community Health Survey-Mental Health and Well-Being, consisting of adults aged 15 years or older (n = 36 984), were linked to Canadian 2001 Census profiles according to health region boundaries (n = 97). Multilevel multivariable logistic regression modelling was used to: estimate variation in 12-month self-reported use of health services for mental health reasons between health regions; and, estimate the effects of individual- and area-level need, health resources, and sociodemographic factors on self-reported 12-month use of medical services for mental health reasons., Results: There was a 2.1% and 3.5% regional variation for general practitioner-family physician (GP-FP) and psychiatric health service use during 12 months, respectively. Most of the regional variation observed was explained by number of physicians per health region and regional and individual need factors. Adults who were middle-aged, had a post-secondary education, low-income, were separated, widowed, or divorced, and Canadian-born were significantly more likely to use GP-FP and psychiatry services for mental health reasons at the individual level, even after adjusting for area- and individual-level need factors., Conclusions: Most area-level variation was explained by the availability of health region resources and individual-level need factors. After accounting for need, numerous sociodemographic factors retained their association with use of mental health services. Additional efforts are needed at the area and individual level to reduce inequities through appropriate targeted care.

Gender inequities in health prevail in most countries despite ongoing attempts to eliminate them. Assessment of gender-sensitive health policies can be used to identify country specific progress as well as gaps and issues that need to be addressed to meet health equity goals. This study selected and measured the existence of gender-sensitive health policies in a low- (Peru), middle- (Colombia), and high (Canada)-income country in the Americas. Investigators selected 10 of 20 gender-sensitive health policy indicators and found eight to be feasible to measure in all three countries, although the wording and scope varied. The results from this study inform policy makers and program planners who aim to develop, improve, implement, and monitor national gender-sensitive health policies. Future studies should assess the implementation of policy indicators within countries and assess their performance in increasing gender equity.

Background: Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome., Methods: We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes., Discussion: A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.

Background: Depression after stroke occurs in 33% of individuals. It is grossly underdiagnosed and untreated., Objective: The authors studied sex differences in the prevalence of post-stroke depression (PSD), which have not been adequately studied, and may have important implications for clinicians., Method: The authors performed a systematic review of five databases of all observational studies that stratified data by sex, measuring the prevalence of PSD., Results: Fifty-six publications, including 47 primary studies between 1982 and 2006, met eligibility criteria and were included in the review. A total of 75,131 subjects comprised these studies, with 11,910 women and 62,899 men., Results: The prevalence of depression among women was higher in 35 studies. Moreover, the prevalence was generally higher among inpatient populations (both in acute-care and rehabilitation facilities) than in community-dwelling subjects., Conclusions: PSD is highly prevalent in both sexes, but appears to be slightly more common among women than men. Untreated depression after stroke can lead to a reduced quality of life, poorer prognosis, and increased mortality. All stroke patients should be routinely screened for depression, and further research is needed to determine whether there are sex-specific differences in response to treatment.

Background: Survivors of ARDS have well documented physical limitations, but psychological effects are less clear. We determined the prevalence of self-reported depression and memory dysfunction in ARDS survivors., Methods: Six to 48 (median 22) months after ICU discharge, we administered instruments assessing depression symptoms (Beck Depression Inventory-II [BDI-II]) and memory dysfunction (Memory Assessment Clinics Self-Rating Scale [MAC-S]) to 82 ARDS patients who were enrolled in a prospective cohort study in four university-affiliated ICUs., Results: Sixty-one (74%), 64 (78%), and 61 (74%) patients fully completed the BDI-II, MAC-S (Ability subscale), and MAC-S (Frequency of Occurrence subscale) instruments. Responders (similar to nonresponders) were young (median 42 years, interquartile range [IQR] 35 to 56), with high admission illness severity and organ dysfunction. The median BDI-II score was 12 (IQR 5 to 25). Twenty-five (41%) patients reported moderate-severe depression symptoms and were less likely to return to work than those with minimal-mild symptoms (8/25 [32%] vs 25/36 [69%]; p = 0.005). Median MAC-S (Ability) and MAC-S (Frequency of Occurrence) scores were 76 (IQR 61 to 93) and 91 (IQR 77 to 102), respectively; 8%, 16%, and 20% scored > 2, > 1.5, and > 1 SD(s), respectively, below age-adjusted population norms for each subscale. BDI-II and MAC-S scores were negatively correlated (Spearman coefficient -0.58 and -0.50 for Ability and Frequency of Occurrence subscales, respectively; p < 0.0001). Univariable analyses showed no demographic or illness-severity predictors of BDI-II (including the Cognitive subscale) or MAC-S (both subscales); results were similar when restricted to patients whose primary language was English., Conclusions: ARDS survivors report a high prevalence of depression symptoms and a lower prevalence of memory dysfunction 6 to 48 months after ICU discharge. Depression symptoms may hinder the return to work, or patients may report these symptoms because of inability to re-enter the workforce.

There have been no recent advances in drug development for mood disorders in terms of identifying drug targets that are mechanistically distinct from existing ones. As a result, existing antidepressants are based on decades-old notions of which targets are relevant to the mechanisms of antidepressant action. Low rates of remission, a delay of onset of therapeutic effects, continual residual depressive symptoms, relapses, and poor quality of life are unfortunately common in patients with mood disorders. Offering alternative options is requisite in order to reduce the individual and societal burden of these diseases. The glutamatergic system is a promising area of research in mood disorders, and likely to offer new possibilities in therapeutics. There is increasing evidence that mood disorders are associated with impairments in neuroplasticity and cellular resilience, and alterations of the glutamatergic system are known to play a major role in cellular plasticity and resilience. Existing antidepressants and mood stabilizers have prominent effects on the glutamate system, and modulating glutamatergic ionotropic or metabotropic receptors results in antidepressant-like properties in animal models. Several glutamatergic modulators targeting various glutamate components are currently being studied in the treatment of mood disorders, including release inhibitors of glutamate, N-methyl-D-aspartate (NMDA) antagonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) throughput enhancers, and glutamate transporter enhancers. This paper reviews the currently available knowledge regarding the role of the glutamatergic system in the etiopathogenesis of mood disorders and putative glutamate modulators.

Objectives: To determine the relationship between the premortem and postmortem diagnosis in critically ill bone marrow transplantation patients Also, to evaluate the appropriateness of the reliance on clinical diagnosis for withdrawal of active treatment decision-making., Design: Retrospective cohort study., Setting: Two university-affiliated tertiary care medical surgical intensive care units., Patients: Critically ill bone marrow transplantation patients who died in the intensive care unit between November 1,1994, and June 30,1999, and underwent postmortem examination., Intervention: Review of medical records by two independent data extractors. Clinical diagnosis and cause of death in the intensive care unit were compared with the final autopsy report., Measurements and Main Results: Premortem clinical diagnoses were classified according to the Goldman criteria and compared with postmortem findings. Twenty-eight autopsies were done. Ten of 28 (36%) patients had discrepancies uncovered on autopsy; only two discrepancies would have influenced patient management and none would have altered patient outcome. Twenty patients had their active treatment withdrawn and underwent postmortem examination. None of the discrepancies noted would have altered outcome in these patients., Conclusion: In the bone marrow transplantation population, there is significant concordance between clinical diagnosis and postmortem findings. Reliance on clinical diagnosis may be valid for withdrawal of active treatment decision-making in these patients.

Inhibition of phosphodiesterase (PDE) activity is beneficial in models of arthritis and airway inflammation. Here we assessed the ability of PDE inhibitors to modulate colitis by exposing mice to 4% (w/v) dextran sulfate sodium (DSS) drinking water for 5 days with or without rolipram, an inhibitor of PDE type 4, or the nonselective PDE inhibitor, pentoxifylline (both at 5 mg/kg, i.p., twice daily). Controls received saline, vehicle, or drug only. Colonic histology, myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-alpha) levels, and epithelial ion transport (baseline and stimulated by electrical nerve stimulation, carbachol, and forskolin) were examined. DSS-treated mice displayed a variable diarrhea, significant histopathology in the mid-distal colon, elevated MPO activity, and reduced (>50%) responses to all three pro-secretory stimuli. Treatment with rolipram, and to a lesser extent pentoxifylline, significantly reduced the severity of the colonic histopathology and MPO levels. Neither PDE inhibitor had any affect on the diminished ion transport events caused by DSS-induced colitis. However, although stimulated ion transport events were still reduced 3 days after DSS treatment, colonic segments from DSS + rolipram-treated mice displayed enhanced recovery in their secretory responsiveness, particularly to carbachol. These findings indicate that specific PDE4 inhibition can significantly reduce the tissue damage that accompanies colitis and enhance recovery of normal colonic function.