Brendon Stubbs

Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis

Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta‐analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%‐34.4%; N = 198; n = 52,678). Relative risk meta‐analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta‐analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = −3.6, p = 0.0003, r2 = 0.19). People treated with all individual antipsychotic medications had a significantly (p<0.001) higher MetS risk compared to antipsychotic‐naïve participants. MetS risk was significantly higher with clozapine and olanzapine (except vs. clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs. amisulpride). Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35‐1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices.

Risk of dementia and mild cognitive impairment in older people with subjective memory complaints: meta-analysis.

To investigate whether people with subjective memory complaints (SMC) but no objective deficits are at increased risk of developing mild cognitive impairment (MCI) and dementia.

Exercise as a treatment for depression: A meta-analysis adjusting for publication bias

The effects of exercise on depression have been a source of contentious debate. Meta-analyses have demonstrated a range of effect sizes. Both inclusion criteria and heterogeneity may influence the effect sizes reported. The extent and influence of publication bias is also unknown. Randomized controlled trials (RCTs) were identified from a recent Cochrane review and searches of major electronic databases from 01/2013 to 08/2015. We included RCTs of exercise interventions in people with depression (including those with a diagnosis of major depressive disorder (MDD) or ratings on depressive symptoms), comparing exercise versus control conditions. A random effects meta-analysis calculating the standardized mean difference (SMD, 95% confidence interval; CI), meta-regressions, trim and fill and fail-safe n analyses were conducted. Twenty-five RCTs were included comparing exercise versus control comparison groups, including 9 examining participants with MDD. Overall, exercise had a large and significant effect on depression (SMD adjusted for publication bias = 1.11 (95% CI 0.79-1.43)) with a fail-safe number of 1057. Most adjusted analyses suggested publication bias led to an underestimated SMD. Larger effects were found for interventions in MDD, utilising aerobic exercise, at moderate and vigorous intensities, in a supervised and unsupervised format. In MDD, larger effects were found for moderate intensity, aerobic exercise, and interventions supervised by exercise professionals. Exercise has a large and significant antidepressant effect in people with depression (including MDD). Previous meta-analyses may have underestimated the benefits of exercise due to publication bias. Our data strongly support the claim that exercise is an evidence-based treatment for depression.

Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta-analysis

Type 2 diabetes mellitus (T2DM) is highly predictive of cardiovascular diseases and can have particularly deleterious health impacts in people with severe mental illness (SMI), i.e. schizophrenia, bipolar disorder or major depressive disorder. This meta‐analysis aimed: a) to describe pooled frequencies of T2DM in people with SMI; b) to analyze the influence of demographic, illness and treatment variables as well as T2DM assessment methods; and c) to describe T2DM prevalence in studies directly comparing persons with each specific SMI diagnosis to general population samples. The trim and fill adjusted pooled T2DM prevalence among 438,245 people with SMI was 11.3% (95% CI: 10.0%‐12.6%). In antipsychotic‐naïve participants, the prevalence of T2DM was 2.9% (95% CI: 1.7%‐4.8%). There were no significant diagnostic subgroup differences. A comparative meta‐analysis established that multi‐episode persons with SMI (N=133,470) were significantly more likely to have T2DM than matched controls (N=5,622,664): relative risk, RR=1.85, 95% CI: 1.45‐2.37, p<0.001. The T2DM prevalence was consistently elevated in each of the three major diagnostic subgroups compared to matched controls. Higher T2DM prevalences were observed in women with SMI compared to men (RR=1.43, 95% CI: 1.20‐1.69, p<0.001). Multi‐episode (versus first‐episode) status was the only significant predictor for T2DM in a multivariable meta‐regression analysis (r2=0.52, p<0.001). The T2DM prevalence was higher in patients prescribed antipsychotics, except for aripriprazole and amisulpride. Routine screening and multidisciplinary management of T2DM is needed. T2DM risks of individual antipsychotic medications should be considered when making treatment choices.

Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large‐scale meta‐analysis of 3,211,768 patients and 113,383,368 controls

People with severe mental illness (SMI) – schizophrenia, bipolar disorder and major depressive disorder – appear at risk for cardiovascular disease (CVD), but a comprehensive meta‐analysis is lacking. We conducted a large‐scale meta‐analysis assessing the prevalence and incidence of CVD; coronary heart disease; stroke, transient ischemic attack or cerebrovascular disease; congestive heart failure; peripheral vascular disease; and CVD‐related death in SMI patients (N=3,211,768) versus controls (N=113,383,368) (92 studies). The pooled CVD prevalence in SMI patients (mean age 50 years) was 9.9% (95% CI: 7.4‐13.3). Adjusting for a median of seven confounders, patients had significantly higher odds of CVD versus controls in cross‐sectional studies (odds ratio, OR=1.53, 95% CI: 1.27‐1.83; 11 studies), and higher odds of coronary heart disease (OR=1.51, 95% CI: 1.47‐1.55) and cerebrovascular disease (OR=1.42, 95% CI: 1.21‐1.66). People with major depressive disorder were at increased risk for coronary heart disease, while those with schizophrenia were at increased risk for coronary heart disease, cerebrovascular disease and congestive heart failure. Cumulative CVD incidence in SMI patients was 3.6% (95% CI: 2.7‐5.3) during a median follow‐up of 8.4 years (range 1.8‐30.0). Adjusting for a median of six confounders, SMI patients had significantly higher CVD incidence than controls in longitudinal studies (hazard ratio, HR=1.78, 95% CI: 1.60‐1.98; 31 studies). The incidence was also higher for coronary heart disease (HR=1.54, 95% CI: 1.30‐1.82), cerebrovascular disease (HR=1.64, 95% CI: 1.26‐2.14), congestive heart failure (HR=2.10, 95% CI: 1.64‐2.70), and CVD‐related death (HR=1.85, 95% CI: 1.53‐2.24). People with major depressive disorder, bipolar disorder and schizophrenia were all at increased risk of CVD‐related death versus controls. CVD incidence increased with antipsychotic use (p=0.008), higher body mass index (p=0.008) and higher baseline CVD prevalence (p=0.03) in patients vs. controls. Moreover, CVD prevalence (p=0.007), but not CVD incidence (p=0.21), increased in more recently conducted studies. This large‐scale meta‐analysis confirms that SMI patients have significantly increased risk of CVD and CVD‐related mortality, and that elevated body mass index, antipsychotic use, and CVD screening and management require urgent clinical attention.

How much physical activity do people with schizophrenia engage in? A systematic review, comparative meta-analysis and meta-regression

OBJECTIVE Physical activity (PA) improves health outcomes in people with schizophrenia. It is unclear how much PA people with schizophrenia undertake and what influences PA participation. We conducted a meta-analysis to investigate PA levels and predictors in people with schizophrenia. METHOD Major databases were searched from inception till 02/2016 for articles measuring PA (self-report questionnaire (SRQ) or objective measure (e.g. accelerometer)) in people with schizophrenia, including first episode psychosis (FEP). A random effects meta-analysis and meta-regression analysis were conducted. RESULTS 35 studies representing 3453 individuals with schizophrenia (40.0years; 64.0% male) were included. Engagement in light PA was 80.44min (95% CI 68.32-92.52, n=2658), 47.1min moderate-vigorous PA (95% CI 31.5-62.8, n=559) and 1.05min (95% CI 0.48-1.62, n=2533) vigorous PA per day. People with schizophrenia engaged in significantly less moderate (hedges g=-0.45, 95% CI -0.79 to -0.1, p=0.01) and vigorous PA (g=-0.4, 95% CI -0.60 to -0.18) versus controls. Higher light to moderate, but lower vigorous PA levels were observed in outpatients and in studies utilizing objective measures versus SRQ. 56.6% (95% CI 45.8-66.8, studies=12) met the recommended 150min of moderate physical activity per week. Depressive symptoms and older age were associated with less vigorous PA in meta-regression analyses. CONCLUSIONS Our data confirm that people with schizophrenia engage in significantly less moderate and vigorous PA versus controls. Interventions aiming to increase PA, regardless of intensity are indicated for people with schizophrenia, while specifically increasing moderate-vigorous PA should be a priority given the established health benefits.

Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies

To conduct a systematic review and meta‐analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HCs).

Inflammation and frailty in the elderly: A systematic review and meta-analysis

The pathogenesis of frailty and the role of inflammation is poorly understood. We examined the evidence considering the relationship between inflammation and frailty through a systematic review and meta-analysis. A systematic literature search of papers providing data on inflammatory biomarkers and frailty was carried out in major electronic databases from inception until May 2016. From 1856 initial hits, 35 studies (32 cross-sectional studies n=3232 frail, n=11,483 pre-frail and n=8522 robust, and 563 pre-frail+robust; 3 longitudinal studies n=3402 participants without frailty at baseline) were meta-analyzed. Cross-sectional studies reported that compared to 6757 robust participants, both 1698 frail (SMD=1.00, 95%CI: 0.40-1.61) and 8568 pre-frail (SMD=0.33, 95%CI: 0.04-0.62) participants had significantly higher levels of C-reactive protein (CRP). Frailty (n=1057; SMD=1.12, 95%CI: 0.27-2.13) and pre-frailty (n=4467; SMD=0.56, 95%CI: 0.00-1.11) were associated with higher serum levels of interleukin-6 compared to people who were robust (n=2392). Frailty and pre-frailty were also significantly associated with elevated white blood cell and fibrinogen levels. In three longitudinal studies, higher serum CRP (OR=1.06, 95%CI: 0.78-1.44,) and IL-6 (OR=1.19, 95%CI: 0.87-1.62) were not associated with frailty. In conclusion, frailty and pre-frailty are associated with higher inflammatory parameters and in particular CRP and IL-6. Further longitudinal studies are needed.

Pain and the Risk for Falls in Community-Dwelling Older Adults: Systematic Review and Meta-Analysis

OBJECTIVE To conduct a systematic review and meta-analysis to establish the association between pain and falls in community-dwelling older adults. DATA SOURCES Electronic databases from inception until March 1, 2013, including Cochrane Library, CINAHL, EBSCO, EMBASE, PubMed, and PsycINFO. STUDY SELECTION Two reviewers independently conducted the searches and completed methodological assessment of all included studies. Studies were included that (1) focused on adults older than 60 years; (2) recorded falls over 6 or more months; and (3) identified a group with and without pain. Studies were excluded that included (1) participants with dementia or a neurologic condition (eg, stroke); (2) participants whose pain was caused by a previous fall; or (3) individuals with surgery/fractures in the past 6 months. DATA EXTRACTION One author extracted all data, and this was independently validated by another author. DATA SYNTHESIS A total of 1334 articles were screened, and 21 studies met the eligibility criteria. Over 12 months, 50.5% of older adults with pain reported 1 or more falls compared with 25.7% of controls (P<.001). A global meta-analysis with 14 studies (n=17,926) demonstrated that pain was associated with an increased odds of falling (odds ratio [OR]=1.56; 95% confidence interval [CI], 1.36-1.79; I(2)=53%). A subgroup meta-analysis incorporating studies that monitored falls prospectively established that the odds of falling were significantly higher in those with pain (n=4674; OR=1.71; 95% CI, 1.48-1.98; I(2)=0%). Foot pain was strongly associated with falls (n=691; OR=2.38; 95% CI, 1.62-3.48; I(2)=8%) as was chronic pain (n= 5367; OR=1.80; 95% CI, 1.56-2.09; I(2)=0%). CONCLUSIONS Community-dwelling older adults with pain were more likely to have fallen in the past 12 months and to fall again in the future. Foot and chronic pain were particularly strong risk factors for falls, and clinicians should routinely inquire about these when completing falls risk assessments.

How sedentary are people with psychosis? A systematic review and meta-analysis

OBJECTIVE Sedentary behavior (SB) is an independent risk factor for cardiovascular disease and mortality. We conducted a meta-analysis to investigate SB levels and predictors in people with psychosis. METHOD Major electronic databases were searched from inception till 09/2015 for articles measuring SB with a self-report questionnaire (SRQ) or objective measure (e.g. accelerometer) in people with psychosis, including schizophrenia spectrum and bipolar disorders. A random effects meta-analysis and meta regression analysis were conducted. RESULTS Thirteen studies were eligible including 2033 people with psychosis (mean age 41.3years (range 25.1-60), 63.2% male (range 35-89%), body mass index 28.7 (range 25.9-32.1). The trim and fill analysis demonstrated people with psychosis spent 660.8min (95% CI 523.2-798.4, participants=2033) or 11.0h (95% CI 8.72-13.3) per day being sedentary. Objective measures of SB recorded significantly higher levels (p<0.001) of SB (12.6h per day, 95% CI 8.97-16.2, studies=7, participants=254) compared to self-report SB (6.85h per day, 95% CI 4.75-8.96, studies=6, participants=1779). People with psychosis engaged in significantly more SB than controls (g=1.13, 95% CI 0.496-1.77, P<0.001, n psychosis=216, n controls=159) equating to a mean difference of 2.80 (95% CI 1.47-4.1) hours per day. Multivariate meta-regression confirmed that objective measurement of SB predicted higher levels of sedentariness. CONCLUSIONS People with psychosis engage in very high levels of sedentary behavior in their waking day and current SRQ may underestimate SB. Given that SB is an independent predictor of cardiovascular disease, future interventions specifically targeting the prevention of SB are warranted.