Recanalization and outcomes after cerebral venous thrombosis: a systematic review and meta-analysis.

Background: Recanalization in cerebral venous thrombosis (CVT) can begin as early as 1 week after initiating therapeutic anticoagulation. The clinical significance of recanalization remains uncertain. Objectives: We aimed to investigate the association between recanalization and functional outcomes and explored predictors of recanalization. Methods: A systematic literature search was conducted (EMBASE, MEDLINE, Cochrane library) to identify: (1) patients with CVT aged ≥18 years treated with anticoagulation only; (2) case series, cohort, or randomized controlled trial studies; and (3) reported recanalization rates and functional outcomes using either a modified Rankin Scale (mRS) or sequelae of CVT at last follow-up. Meta-analysis was performed using pooled odds ratios (ORs) with exploration of sex and age effects using meta-regression. Results: Twenty-three studies were eligible with 1418 individual patients in total. Timing of reimaging and clinical reassessment was variable. Absence of recanalization was associated with increased odds of an unfavorable functional outcome (mRS 2-6 versus 0-1; OR, 3.66; 95% CI, 1.73-7.74; p = 0.001), CVT recurrence (OR, 8.81; 95% CI, 1.63-47.7; p = 0.01), and chronic headache (OR, 2.78; 95% CI, 1.16-6.70; p = 0.02). On meta-regression, the relationship between recanalization and mRS differed by the proportion of female patients, where lower proportions of women were associated with higher likelihood of a worse outcome, but not by mean participant age. There was no incremental benefit of full compared with partial recanalization with respect to favorable mRS or recurrence, but odds of chronic headache were higher with partial versus full recanalization (OR, 3.80; 95% CI, 1.43-10.11; p = 0.008). Epilepsy and visual sequelae were not associated with recanalization. Conclusions: Absence of recanalization was associated with worse functional outcomes, CVT recurrence, and headache, but outcomes were modified by sex. The degree of recanalization was significant in relation to headache outcomes, where partial compared with complete recanalization resulted in a greater likelihood of residual headache. Prospective studies with common timing of repeat clinical-neuroimaging assessments will help to better ascertain the relationship and directionality between the degree of recanalization and outcomes.

Insomnia and post-traumatic stress disorder: A meta-analysis on interrelated association (n = 57,618) and prevalence (n = 573,665).

Posttraumatic stress disorder (PTSD) is a common mental disorder, which is strongly associated with insomnia, yet their epidemiological overlap is poorly understood. To determine the convergent quantitative magnitude of their relationship, PubMed, EMBASE, Scopus, Web of Science, PubPsych, and PsycINFO were searched to identify studies that either reported the correlation or frequency of insomnia symptoms in PTSD and posttraumatic stress symptoms (PTSS), or both. Out of 3714 records, 75 studies met selection criteria and aggregate effect size (ES) estimates were generated for the correlations (K=44, comprising 57,618 subjects) and frequencies (K=33, comprising 573,665 subjects with PTSD/PTSS) of insomnia symptoms in PTSD/PTSS. A medium-size significant correlation was found [ES: 0.52 (CI: 0.47-0.57)] with moderating effects of the COVID-19 pandemic and military service as causes of trauma. The prevalence of insomnia in PTSD/PTSS was 63% [CI: 45%-78%] and was moderated by the cause of trauma as well as the PTSD/PTSS assessment scale. The findings from this meta-analysis highlight the importance of screening and managing insomnia in PTSD patients.

Hemorrhagic Transformation in Acute Ischemic Stroke: A Quantitative Systematic Review.

The prevalence and risk factors of hemorrhagic transformation (HT) after acute ischemic stroke HT have not been adequately delineated. We performed a systematic review and meta-analysis to identify English-language prospective observational MEDLINE and EMBASE-listed reports of acute ischemic stroke with HT published from 1985-2017. Studies that used the ECASS-2 definitions of hemorrhagic transformation subtypes, hemorrhagic infarction (HI), and parenchymal hematoma (PH) were included. Patients treated with intravenous thrombolysis with tissue plasminogen activator (IV-tPA) were compared with those who did not receive thrombolysis. A total of 65 studies with 17,259 patients met inclusion criteria. Overall, HT prevalence was 27%; 32% in patients receiving IV-tPA vs. 20% in those without. Overall PH prevalence was 9%; 12% in IV-tPA treated patients vs. 5% in those without. HT was associated with a history of atrial fibrillation (OR 2.94) and use of anticoagulants (OR 2.47). HT patients had higher NIHSS (Hedge's-G 0.96) and larger infarct volume (diffusion-weighted MRI, Hedge's-G 0.8). In IV-tPA treated patients, PH correlated with antiplatelet (OR 3) and statin treatment (OR 4). HT (OR 3) and PH (OR 8) were associated with a poor outcome at 90-day (mRS 5-6). Hemorrhagic transformation is a frequent complication of acute ischemic stroke and is associated with poor outcome. Recognition of risk factors for HT and PH may reduce their incidence and severity.

Basilar Apex Aneurysm: Case Series, Systematic Review, and Meta-analysis.

BACKGROUND: A lower rate of aneurysmal recanalization in stent assisted coiling versus coiling alone has been observed in aneurysms overall. This study aims to primarily stratify and compare degree of occlusion per treatment modality in basilar apex aneurysms. Secondary outcomes were retreatment, posttreatment hemorrhage, and procedure-related complications. METHODS: Medical literature including MEDLINE and EMBASE database was searched. We performed metaregressions, bias analysis, and fail-safe N. We controlled for the quality of the studies. RESULTS: Data from eligible studies (N = 12) and study center patients (n = 117) were pooled for a total of 396 nonduplicated patients. Stent-assisted coiling had a lower rate of retreatment (17% vs. 24%) and higher rate of posttreatment hemorrhage (5% vs. 3%) compared with coiling. Stent-assisted coiling had a higher rate of complete occlusion (55% vs. 45%) and a lower rate of residual aneurysm (15% vs. 23%) compared with coiling. Comparative analyses were performed. Microsurgical technique remained the most morbid treatment modality with the best rate of complete occlusion (93%) and lowest rates of rehemorrhage (2%) and retreatment (5%). CONCLUSIONS: This is the first and largest meta-analysis focused on patients treated for basilar apex aneurysm. We report higher rehemorrhage rates with stent-assisted coiling. This study provides benchmark data to guide clinicians in future treatment decision making and encourages future research to stratify outcomes.

Effects of Ketamine Anesthesia on Efficacy, Tolerability, Seizure Response, and Neurocognitive Outcomes in Electroconvulsive Therapy: A Comprehensive Meta-analysis of Double-Blind Randomized Controlled Trials.

Electroconvulsive therapy (ECT) remains the most effective treatment for major depressive disorder. Ketamine is an anesthetic gaining attention for its rapid antidepressant effect. Numerous randomized controlled trials have investigated the effect of ketamine anesthesia in ECT on various clinical outcomes. Previous systematic reviews have not found benefit for overall depression response, although some have found evidence of benefit early in the ECT course. Clear quantitative conclusions have not been established regarding other outcomes, particularly while only using data from high-quality studies. We aimed to examine all data from double-blind randomized controlled trials comparing ketamine to other anesthetics via meta-analysis, to make recommendations regarding ECT practice and future research. Data were extracted for depressive symptoms, seizure duration and electrical dose, neuropsychological performance, and adverse effects. Effect sizes were calculated using Hedge's g and odds ratios. Eighteen studies (n = 915) were included in the meta-analysis. Ketamine was not found to enhance improvement of depressive symptoms, either early in ECT course or at end of study. Ketamine had a large effect on increasing seizure duration both overall (Hedge's g = 0.71, P = 0.038) and in the subgroup receiving ketamine in combination with another anesthetic (Hedge's g = 0.78, P < 0.01), and on decreasing electrical dose (Hedge's g = 1.98, P = 0.039). There was no significant effect of ketamine on any individual neuropsychological domain. Ketamine was not associated with increased adverse effects, except for hypertension in patients receiving ketamine monotherapy. Significant heterogeneity was present for many outcomes, and sensitivity analyses suggested a relation to methodological variation in most cases. This study supports the finding that ketamine does not enhance ECT's antidepressant effect, including on early improvement, but provides substantial evidence for enhancing seizure duration and reducing electrical dose. No significant benefit was found on neurocognitive outcomes, but analysis was limited by small sample sizes and high heterogeneity. Ketamine is generally safe in ECT, particularly as a coanesthetic. Our findings provide meta-analytic support to the recommendations in ECT clinical guidelines for use of coadjuvant ketamine in ECT where seizures are suboptimal. Further studies targeting neurocognitive outcomes are encouraged.

Neuroimaging insights into the link between depression and Insomnia: A systematic review.

BACKGROUND: Insomnia is a common symptom of Major Depressive Disorder (MDD) and genome-wide association studies pointed to their strong genetic association. Although the prevalence of insomnia symptoms in MDD is noticeable and evidence supports their strong bidirectional association, the number of available neuroimaging findings on patients of MDD with insomnia symptoms is limited. However, such neuroimaging studies could verily improve our understanding of their shared pathophysiology and advance corresponding theories. METHODS: Based on the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guideline, we have conducted a literature search using PubMed, EMBASE, and Scopus databases and systematically explored 640 studies using various neuroimaging modalities in MDD patients with different degrees of insomnia symptoms. RESULTS: Despite inconsistencies, current findings from eight studies suggested structural and functional disturbances in several brain regions including the amygdala, prefrontal cortex and anterior cingulate cortex and insula. The aberrant functional connectivity within and between the main hubs of the salience and default mode networks could potentially yield new insights into the link between MDD and insomnia, which needs further assessment. LIMITATIONS: The number of studies reviewed herein is limited. The applied methods for assessing structural and functional neural mechanisms of insomnia and depression were variable. CONCLUSION: Neuroimaging methods demonstrated the overlapping underlying neural mechanisms between MDD and insomnia. Future studies may facilitate better understanding of their pathophysiology to allow development of specific treatment.

Practical recommendations to conduct a neuroimaging meta-analysis for neuropsychiatric disorders.

Over the past decades, neuroimaging has become widely used to investigate structural and functional brain abnormality in neuropsychiatric disorders. The results of individual neuroimaging studies, however, are frequently inconsistent due to small and heterogeneous samples, analytical flexibility, and publication bias toward positive findings. To consolidate the emergent findings toward clinically useful insight, meta-analyses have been developed to integrate the results of studies and identify areas that are consistently involved in pathophysiology of particular neuropsychiatric disorders. However, it should be considered that the results of meta-analyses could also be divergent due to heterogeneity in search strategy, selection criteria, imaging modalities, behavioral tasks, number of experiments, data organization methods, and statistical analysis with different multiple comparison thresholds. Following an introduction to the problem and the concepts of quantitative summaries of neuroimaging findings, we propose practical recommendations for clinicians and researchers for conducting transparent and methodologically sound neuroimaging meta-analyses. This should help to consolidate the search for convergent regional brain abnormality in neuropsychiatric disorders.

Link between insomnia and perinatal depressive symptoms: A meta-analysis.

Evidence shows the possible link between insomnia and perinatal depressive symptoms. In order to find a convergent quantitative answer, we collected data via the search of Medline, EMBASE and reference tracking, which included nine studies (a total sample of 1,922 women). An aggregate effect size estimate (correlation coefficient) was generated using the comprehensive meta-analysis software. For the meta-analytic procedure, a random effects model was set a priori. Moderating factors, including study design, method of assessment of depression, geographical origin of data, publication year, mean age, % married, breastfeeding rate, quality and type of data, % primiparous and history of depression, were examined via categorical or univariate mixed-effects (method of moments) meta-regression methods. Heterogeneity and publication bias were examined using standard meta-analytic approaches. We found a significant, medium-size relationship between insomnia and perinatal depressive symptoms (point estimate, 0.366; 95% confidence interval [CI], 0.205-0.508; p < 0.001; n = 9) and this was significantly heterogeneous (Q, 118.77; df, 8; p < 0.001; I2 , 93.26%). The effect size estimate was significant for studies reporting no history of depression (point estimate, 0.364; 95% CI, 0.035-0.622; p < 0.05; n = 5) and for study design. With meta-regression, no moderating factor (age, marriage rate, breastfeeding rate, pregnancy history or publication year) significantly mediated the effect size estimate. The depression assessment scale used, but not other categorical variables, explained the magnitude of heterogeneity. We found that insomnia during the perinatal period is associated with depressive symptoms, which warrants screening pregnant mothers for insomnia and depression.

Prevalence of delusions in drug-naïve Alzheimer disease patients: A meta-analysis.

INTRODUCTION: Neuropsychiatric symptoms (NPS) are common at all stages of Alzheimer disease (AD). Delusions in AD are associated with negative clinical consequences and may signal rapid disease progression. Hence, we sought to determine the prevalence of delusions in drug-naïve (no cholinesterase inhibitor or neuroleptic medications) AD patients. METHODS: In this meta-analysis, a search of the EMBASE, MEDLINE, and PsycINFO databases was performed. We selected studies reporting delusion prevalence measured by the Neuropsychiatric Inventory (NPI) in drug-naïve AD patients. An aggregate delusion event rate with 95% confidence interval (CI) was calculated. The I2 statistic was used to assess the magnitude of between-study heterogeneity. Single variable meta-regressions allowed examination of the effect of moderating factors and heterogeneity. Quantitative measures were used to appraise for publication bias. RESULTS: We identified 6 studies with 591 participants allowing calculation of the aggregate delusional prevalence rate. Irrespective of dementia severity, the aggregate event rate for delusions was 29.1% (95% CI: 20-41%; I2  = 84.59). No publication bias was observed. CONCLUSION: This meta-analysis calculates a 29.1% prevalence rate of delusions in AD patients. There is a trend towards increasing delusion prevalence in concordance with increasing severity of dementia. Given delusions are associated with poorer outcomes, the obtained prevalence should motivate clinicians to screen carefully for delusions. Current literature limitations warrant future studies, with sub-analyses on dementia severity, and other neurobiological factors known to influence the presence of delusions.

The Impact of Left Ventricular Assist Device Infections on Postcardiac Transplant Outcomes: A Systematic Review and Meta-Analysis.

Left ventricular assist devices (LVADs) are associated with numerous short- and long-term complications, including infection. The impact LVAD infections have on clinical outcomes after transplantation is not well established. We sought to determine whether the presence of infection while on LVAD support negatively influences outcomes after cardiac transplantation. We searched electronic databases and bibliographies for full text studies that identified LVAD infections during support and also reported on posttransplant outcomes. A meta-analysis of posttransplant survival was conducted using a random effects model. Of 2,373 records, 13 bridge to transplant (BTT) cohort studies were selected (n = 6,631, 82% male, mean age 50.7 ± 2.7 years). A total of 6,067 records (91.5%) received transplant. There were 3,718 (56.1%) continuous-flow LVADs (CF-LVADs), 1,752 (26.4%) pulsatile LVADs, and 1,161 (17.5%) unknown type records. A total of 2,586 records (39.0%) developed LVAD infections. Patients with LVAD infections were younger (50.5 ± 1.5 vs. 51.3 ± 1.5, p = 0.02), had higher body mass indeices (BMIs) (28.4 ± 0.7 vs. 26.8 ± 0.4, p < 0.01), and longer LVAD support times (347.0 ± 157.6 days vs. 180.2 ± 106.0 days, p < 0.01). Meta-analysis demonstrated increased posttransplant mortality in those patients who had an LVAD infection (hazard ratio [HR] 1.30, 95% CI: 1.16-1.46, p < 0.001). Subgroup meta-analyses by continuous-flow and pulsatile device type demonstrated significant increased risk of death for both types of devices (HR 1.47, 95% CI: 1.22-1.76, p < 0.001 and 1.71, 95% CI: 1.19-2.45, p = 0.004, respectively). Patients who develop LVAD infections are younger, have higher BMIs and longer LVAD support times. Our data suggests that LVAD-related infections result in a 30% increase in postcardiac transplantation mortality. Strategies to prevent LVAD infections should be implemented to improve posttransplant outcomes in this high-risk population.

The 2002 NIMH Provisional Diagnostic Criteria for Depression of Alzheimer's Disease (PDC-dAD): Gauging their Validity over a Decade Later.

Presented herein is evidence for criterion, content, and convergent/discriminant validity of the NIMH-Provisional Diagnostic Criteria for depression of Alzheimer's Disease (PDC-dAD) that were formulated to address depression in Alzheimer's disease (AD). Using meta-analytic and systematic review methods, we examined criterion validity evidence in epidemiological and clinical studies comparing the PDC-dAD to Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV), and International Classification of Disease (ICD 9) depression diagnostic criteria. We estimated prevalence of depression by PDC, DSM, and ICD with an omnibus event rate effect-size. We also examined diagnostic agreement between PDC and DSM. To gauge content validity, we reviewed rates of symptom endorsement for each diagnostic approach. Finally, we examined the PDC's relationship with assessment scales (global cognition, neuropsychiatric, and depression definition) for convergent validity evidence. The aggregate evidence supports the validity of the PDC-dAD. Our findings suggest that depression in AD differs from other depressive disorders including Major Depressive Disorder (MDD) in that dAD is more prevalent, with generally a milder presentation and with unique features not captured by the DSM. Although the PDC are the current standard for diagnosis of depression in AD, we identified the need for their further optimization based on predictive validity evidence.

Differentiation chronic post traumatic stress disorder patients from healthy subjects using objective and subjective sleep-related parameters.

Sleep disturbance is common in chronic post-traumatic stress disorder (PTSD). However, prior work has demonstrated that there are inconsistencies between subjective and objective assessments of sleep disturbance in PTSD. Therefore, we investigated whether subjective or objective sleep assessment has greater clinical utility to differentiate PTSD patients from healthy subjects. Further, we evaluated whether the combination of subjective and objective methods improves the accuracy of classification into patient versus healthy groups, which has important diagnostic implications. We recruited 32 chronic war-induced PTSD patients and 32 age- and gender-matched healthy subjects to participate in this study. Subjective (i.e. from three self-reported sleep questionnaires) and objective sleep-related data (i.e. from actigraphy scores) were collected from each participant. Subjective, objective, and combined (subjective and objective) sleep data were then analyzed using support vector machine classification. The classification accuracy, sensitivity, and specificity for subjective variables were 89.2%, 89.3%, and 89%, respectively. The classification accuracy, sensitivity, and specificity for objective variables were 65%, 62.3%, and 67.8%, respectively. The classification accuracy, sensitivity, and specificity for the aggregate variables (combination of subjective and objective variables) were 91.6%, 93.0%, and 90.3%, respectively. Our findings indicate that classification accuracy using subjective measurements is superior to objective measurements and the combination of both assessments appears to improve the classification accuracy for differentiating PTSD patients from healthy individuals.

Pharmacological Therapy for Apathy in Alzheimer's Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Apathy is highly prevalent in Alzheimer's disease (AD), but whether pharmacotherapy is effective in managing apathy is unclear. METHODS: To assess the efficacy of pharmacotherapy for apathy in AD we searched for randomized controlled trials (RCT) and aggregate data reporting on apathy in several search engines, reference lists of articles, and reviews. Demographic characteristics and relevant data were extracted to assess apathy. RESULTS: Fifteen RCTs' were examined, and 11 were used in aggregate meta-analytic statistics. Drugs included were cholinesterase inhibitors, memantine, and psycho-stimulants. We found no significant treatment effect in favour of any of the drugs, and the effect-size estimates under a random effect model were heterogeneous. Most RCTs had a high attrition rate and used the NPI apathy subscale to measure apathy. CONCLUSION: The lack of an effect could be explained by methodological limitations, publication bias, and heterogeneity.

Microbleeds in Alzheimer's Disease: A Neuropsychological Overview and Meta-Analysis.

The current literature on the role of brain microbleeds (MB) on the neuropsychological outcomes of Alzheimer's disease (AD) is heterogeneous. We therefore meta-analytically examined the neuropsychological literature pertaining to MBs in AD. Using a priori selected criteria, studies with cross-sectional neuropsychological assessment on MBs and AD were reviewed. Six of 122 studies met selection criteria and provided neuropsychological data on either AD with MB and without MB, or in contrast to healthy controls. The global neuropsychological difference between AD with MB and AD without MB based on random effect model was nonsignificant, heterogeneous, and small (Effect Size =-0.155; 95% confidence interval =-0.465 to 0.155; p value =0.326; Heterogenity: Q-value =12.744; degrees of freedom =5; p =0.026; I2 =61%). The contribution of MBs to cognitive deficits in AD remains unclear. Future studies of MB in AD should strive to use standardized neuroimaging techniques with high sensitivity for MB, a common standard for MB definition, and neuropsychological tests sensitive for detecting subtle cognitive impairment.

Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation: A meta-analysis and systematic review of randomized controlled trials.

Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin-angiotensin-aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin-angiotensin-aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive.A pooled study of 6 randomized controlled trials assessing the efficacy of renin-angiotensin-aldosterone blockers on subjects with atrial fibrillation was performed.A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76- 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70-0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2-2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0-6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0-0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: -0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction.This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation.

The Association Between Obstructive Sleep Apnea and Alzheimer's Disease: A Meta-Analysis Perspective.

Alzheimer's disease (AD) and obstructive sleep apnea (OSA) are highly prevalent, chronic conditions with intriguing, yet poorly understood epidemiological overlap. To date, the amount of OSA syndrome present in patients with AD across literature remains unknown. To address this question, we collected all available published clinical data and analyzed them through a quantitative meta-analytical approach. The results of our quantitative meta-analysis suggest that the aggregate odds ratio for OSA in AD vs. healthy control was 5.05 and homogeneous. This reflects that patients with AD have a five times higher chance of presenting with OSA than cognitively non-impaired individuals of similar age. Moreover, these data suggest that around half of patients with AD have experienced OSA at some point after their initial diagnosis. The additive impact of progressive changes in sleep quality and structure, changes in cerebral blood flow and the cellular redox status in OSA patients may all be contributing factors to cognitive decline and may further aggravate AD progression. It is hoped that the high OSA rate in AD patients, as suggested by the findings of our meta-analysis, might provide a sufficient clinical incentive to alert clinicians the importance of screening patients for OSA in AD, and stimulate further research in this area.

Structural and functional neural adaptations in obstructive sleep apnea: An activation likelihood estimation meta-analysis.

Obstructive sleep apnea (OSA) is a common multisystem chronic disorder. Functional and structural neuroimaging has been widely applied in patients with OSA, but these studies have often yielded diverse results. The present quantitative meta-analysis aims to identify consistent patterns of abnormal activation and grey matter loss in OSA across studies. We used PubMed to retrieve task/resting-state functional magnetic resonance imaging and voxel-based morphometry studies. Stereotactic data were extracted from fifteen studies, and subsequently tested for convergence using activation likelihood estimation. We found convergent evidence for structural atrophy and functional disturbances in the right basolateral amygdala/hippocampus and the right central insula. Functional characterization of these regions using the BrainMap database suggested associated dysfunction of emotional, sensory, and limbic processes. Assessment of task-based co-activation patterns furthermore indicated that the two regions obtained from the meta-analysis are part of a joint network comprising the anterior insula, posterior-medial frontal cortex and thalamus. Taken together, our findings highlight the role of right amygdala, hippocampus and insula in the abnormal emotional and sensory processing in OSA.

Prazosin for treating sleep disturbances in adults with posttraumatic stress disorder: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is a disorder with significant sleep morbidity and limited treatment options. Prazosin may constitute a novel management approach and has been tested recently in a number of trials. We conducted a meta-analysis to examine the effectiveness of prazosin for nightmares and other sleep disturbances in adults with PTSD. METHOD: A systematic review of databases for randomized, double-blind, placebo-controlled trials of adults diagnosed with PTSD and reporting sleep disturbances that were treated with prazosin was conducted in January 2015. No limitations were placed on language or year of publication. RESULTS: Six randomized controlled trials of prazosin for sleep disturbances in patients with PTSD were included (sample n=240). We found that prazosin was statistically significantly more effective than placebo in improving sleep quality [g=0.987, 95% confidence interval (CI): 0.324-1.651] and in reducing overall PTSD symptoms (g=0.699, 95% CI: 0.139-1.260) and sleep disturbances in particular (g=0.799, 95% CI: 0.391-1.234). CONCLUSIONS: Prazosin showed medium-to-large and statistically significant effects on PTSD symptoms in general and sleep disturbances in particular. While promising, results should be interpreted with caution given the limited total number of participants and the limitations induced by the majority of participants being male and noncivilian.

Do antipsychotics prevent postoperative delirium? A systematic review and meta-analysis.

OBJECTIVE: To summarize the effect of antipsychotics for preventing postoperative delirium. DESIGN: We conducted a literature search using Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and clinicaltrials.gov. We included randomized controlled trials of adults undergoing surgery who were given antipsychotics to prevent postoperative delirium. Quality was assessed via the Cochrane risk of bias tool. Random-effects meta-analysis and meta-regression were conducted. Q-statistics and I(2) were used for assessment of heterogeneity. The main outcome was delirium incidence using validated definitions. RESULTS: A total of 1710 subjects were included, with a mean age ranging from 60.7 to 86.4 years. Antipsychotics reduced the incidence of postoperative delirium with the global effect-size estimate (weighted odds ratio) using the random effects model of 0.44 (95% confidence interval: 0.28-0.70; N = 6; Q-value: 16, p-value 0.0005; I(2) = 69%). Significant heterogeneity existed with the pooled global effect of delirium incidence; however, meta-regression allowed us to test both treatment-level and patient-level explanations for significant between-study variance. Baseline risk for delirium was found to be a significant contributor to study heterogeneity, and meta-regression suggested that antipsychotic type and dosage were two of the several treatment-level factors that also may have led to heterogeneity. Our analysis implied the presence of a breakeven baseline level of delirium risk below which preventive treatment with antipsychotics might prove ineffective. CONCLUSIONS: Within the limits of few randomized controlled trials, antipsychotics appeared to reduce the incidence of postoperative delirium in several surgical settings, predominantly orthopedic and for those at higher risk for delirium.