Natalia Diaz-Granados

What Is Resilience

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.

Credibility of claims of subgroup effects in randomised controlled trials: systematic review

Objective To investigate the credibility of authors’ claims of subgroup effects using a representative sample of recently published randomised controlled trials. Design Systematic review. Data source Core clinical journals, as defined by the National Library of Medicine, in Medline. Study selection Randomised controlled trials published in 2007. Using prespecified criteria, teams of trained reviewers independently judged whether authors claimed subgroup effects and the strength of their claims. Reviewers assessed each of these claims against 10 predefined criteria, developed through a search of existing criteria and a consensus process. Results Of 207 randomised controlled trials reporting subgroup analyses, 64 (31%) made claims for the primary outcome. Of those, 20 were strong claims and 28 claims of a likely effect. Authors included subgroup variables measured at baseline in 60 (94%) trials, used subgroup variable as a stratification factor at randomisation in 13 (20%), clearly prespecified their hypotheses in 26 (41%), correctly prespecified direction in 4 (6%), tested a small number of hypotheses in 28 (44%), carried out a test of interaction that proved statistically significant in 6 (9%), documented replication of a subgroup effect with previous related studies in 21 (33%), identified consistency of a subgroup effect across related outcomes in 19 (30%), and provided a compelling indirect evidence for the effect in 14 (22%). In the 19 trials making more than one claim, only one (5%) checked the independence of the interaction. Of the 64 claims, 54 (84%) met four or fewer of the 10 criteria. For strong claims, more than 50% failed each of the individual criteria, and only three (15%) met more than five criteria. Conclusion Authors often claim subgroup effects in their trial report. However, the credibility of subgroup effects, even when claims are strong, is usually low. Users of the information should treat claims that fail to meet most criteria with scepticism. Trial researchers should report the conduct of subgroup analyses and provide sufficient evidence when claiming a subgroup effect or suggesting a possible effect.

Dextran Sulfate Sodium-Induced Colonic Histopathology, but not Altered Epithelial Ion Transport, Is Reduced by Inhibition of Phosphodiesterase Activity

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.

The influence of study characteristics on reporting of subgroup analyses in randomised controlled trials: systematic review

Objective To investigate the impact of industry funding on reporting of subgroup analyses in randomised controlled trials. Design Systematic review. Data sources Medline. Study selection Randomised controlled trials published in 118 core clinical journals (defined by the National Library of Medicine) in 2007. 1140 study reports in a 1:1 ratio by high (five general medicine journals with largest number of total citations in 2007) versus lower impact journals, were randomly sampled. Two reviewers, independently and in duplicate, used standardised, piloted forms to screen study reports for eligibility and to extract data. They also used explicit criteria to determine whether a randomised controlled trial reported subgroup analyses. Logistic regression was used to examine the association of prespecified study characteristics with reporting versus not reporting of subgroup analyses. Results 469 randomised controlled trials were included, of which 207 (44%) reported subgroup analyses. High impact journals (adjusted odds ratio 2.64, 95% confidence interval 1.62 to 4.33), non-surgical (versus surgical) trials (2.10, 1.26 to 3.50), and larger sample size (3.38, 1.64 to 6.99) were associated with more frequent reporting of subgroup analyses. The strength of association between trial funding and reporting of subgroups differed in trials with and without statistically significant primary outcomes (interaction P=0.02). In trials without statistically significant results for the primary outcome, industry funded trials were more likely to report subgroup analyses (2.29, 1.30 to 4.72) than non-industry funded trials. This was not true for trials with a statistically significant primary outcome (0.79, 0.46 to 1.36). Industry funded trials were associated with less frequent prespecification of subgroup hypotheses (31.3% v 38.0%, adjusted odds ratio 0.49, 0.26 to 0.94), and less use of the interaction test for analyses of subgroup effects (41.4% v 49.1%, 0.52, 0.28 to 0.97) than non-industry funded trials. Conclusion Industry funded randomised controlled trials, in the absence of statistically significant primary outcomes, are more likely to report subgroup analyses than non-industry funded trials. Industry funded trials less frequently prespecify subgroup hypotheses and less frequently test for interaction than non-industry funded trials. Subgroup analyses from industry funded trials with negative results for the primary outcome should be viewed with caution.

Cognitive Behavioral Therapy Age Effects in Child and Adolescent Anxiety: An Individual Patient Data Metaanalysis

Investigations of age effects on youth anxiety outcomes in randomized trials (RCTs) of cognitive behavior therapy (CBT) have failed to yield a clear result due to inadequate statistical power and methodologic weaknesses. We conducted an individual patient data metaanalysis to address this gap.

Randomized trials published in higher vs. lower impact journals differ in design, conduct, and analysis

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.

Self-reported Depressive Symptoms and Memory Complaints in Survivors Five Years After ARDS

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.

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials.

BackgroundSubgroup 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 studys primary outcome.MethodsWe 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.DiscussionA 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.

Regional and Individual Influences on Use of Mental Health Services in Canada

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.

Postdischarge Care for Depression in Ontario

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.