Usefulness of aqueous and vitreous humor analysis in infectious uveitis.

OBJECTIVE: To evaluate the role of intraocular fluid analysis as a diagnostic aid for uveitis. METHODS: Twenty-eight samples (27 patients including 3 HIV-infected patients) with active (n=24) or non-active (n=4) uveitis were submitted to aqueous (AH; n=12) or vitreous humor (VH) analysis (n=16). All samples were analyzed by quantitative PCR for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Toxoplasma gondii. RESULTS: The positivity of the PCR in AH was 41.7% (5/12), with 50% (2/4) in immunocompetent and 67% (2/3) in HIV+ patients. The positivity of the PCR in VH was 31.2% (5/16), with 13% (1/8) in immunocompetent and 50% (4/8) in immunosuppressed HIV negative patients. The analysis was a determinant in the diagnostic definition in 58% of HA and 50% of VH. CONCLUSION: Even in posterior uveitis, initial AH analysis may be helpful. A careful formulation of possible clinical diagnosis seems to increase the chance of intraocular sample analysis being meaningful.

Usefulness of aqueous and vitreous humor analysis in infectious uveitis

OBJECTIVE: To evaluate the role of intraocular fluid analysis as a diagnostic aid for uveitis. METHODS: Twenty-eight samples (27 patients including 3 HIV-infected patients) with active (n=24) or non-active (n=4) uveitis were submitted to aqueous (AH; n=12) or vitreous humor (VH) analysis (n=16). All samples were analyzed by quantitative PCR for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Toxoplasma gondii. RESULTS: The positivity of the PCR in AH was 41.7% (5/12), with 50% (2/4) in immunocompetent and 67% (2/3) in HIV+ patients. The positivity of the PCR in VH was 31.2% (5/16), with 13% (1/8) in immunocompetent and 50% (4/8) in immunosuppressed HIV negative patients. The analysis was a determinant in the diagnostic definition in 58% of HA and 50% of VH. CONCLUSION: Even in posterior uveitis, initial AH analysis may be helpful. A careful formulation of possible clinical diagnosis seems to increase the chance of intraocular sample analysis being meaningful.

Clinical relevance of protruded retinal layers in minimum rim width measurement of the optic nerve head.

BACKGROUND/AIMS: Optical coherence tomography (OCT) imaging of the optic nerve head minimum rim width (MRW) has recently been shown to sometimes contain components besides extended retinal nerve fibre layer (RNFL). This study was conducted to determine whether excluding these components, termed protruded retinal layers (PRLs), from MRW increases diagnostic accuracy for detecting glaucoma. METHODS: In this cross-sectional study, we included 123 patients with glaucoma and 123 normal age-similar controls with OCT imaging of the optic nerve head (24 radial scans) and RNFL (circle scan). When present, PRLs were manually segmented, and adjusted MRW measurements were computed. We compared diagnostic accuracy of adjusted versus unadjusted MRW measurement. We also determined whether adjusted MRW correlates better with RNFL thickness compared with unadjusted MRW. RESULTS: The median (IQR) visual field mean deviation of patients and controls was -4.4 (-10.3 to -2.1) dB and 0.0 (-0.6 to 0.8) dB, respectively. In the 5904 individual B-scans, PRLs were identified less frequently in patients (448, 7.6%) compared with controls (728, 12.3%; p<0.01) and were present most frequently in the temporal sector of both groups. Areas under the receiver operating characteristic curves and sensitivity values at 95% specificity indicated that PRL adjustment did not improve diagnostic accuracy of MRW, globally or temporally. Furthermore, adjusting MRW for PRL did not improve its correlation with RNFL thickness in either group. CONCLUSION: While layers besides the RNFL are sometimes included in OCT measurements of MRW, subtracting these layers does not impact clinical utility.

Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders.

(Reprinted with permission from PLoS ONE, (8)5: e63773, 2013).

Risk of Irritability With Psychostimulant Treatment in Children With ADHD: A Meta-Analysis.

OBJECTIVE: Irritability is listed as a common side effect of psychostimulant medications. However, psychostimulants have been demonstrated as an effective treatment in reducing irritability and aggression in children with attention-deficit/hyperactivity disorder (ADHD). The goal of this study was to quantify the risk of irritability as a side effect of psychostimulant treatment for ADHD. DATA SOURCES AND STUDY SELECTION: A PubMed search was conducted on August 18, 2013, to identify all double-blind, randomized, placebo-controlled trials published in English examining the efficacy of psychostimulant medications in the treatment of children with ADHD. Trials were excluded if (1) they required additional psychiatric or medical comorbidity in addition to ADHD, (2) they involved fewer than 20 subjects (parallel group trials), or (3) children received psychostimulant medication for less than 1 week. DATA EXTRACTION: A fixed-effects meta-analysis was used to examine the risk ratio of irritability reported as a side effect in children treated with psychostimulants compared to placebo. Stratified subgroup analysis and meta-regression were used to examine the effects of stimulant type, dosage, duration of use, and trial design on the measured risk of irritability. RESULTS: From 92 potentially eligible trials, the meta-analysis identified 32 trials involving 3,664 children with ADHD that reported data on irritability as a side effect. The relative risk of irritability significantly differed between psychostimulant classes (test for subgroup differences χ²1 = 7.6, P = .006). Methylphenidate derivatives were associated with a significantly decreased risk of irritability compared to placebo (risk ratio [RR] = 0.89 [95% CI, 0.82 to 0.96], z = -2.87, P = .004, k = 32, I² = 50%), whereas amphetamine derivatives were associated with a significantly increased risk of irritability (RR = 2.90 [95% CI, 1.26 to 6.71], z = 2.5, P = .01, k = 5, I² = 0%). CONCLUSIONS: This meta-analysis suggests an increased risk of irritability may be confined to amphetamine-derived psychostimulants. Future meta-analyses examining the effects of amphetamine and methylphenidate derivatives on irritability as a continuous measure, as well as head-to-head trials between methylphenidate and amphetamine derivatives examining effects on irritability, will be important to replicate the findings of this meta-analysis.

Meta-Analysis: Reduced Risk of Anxiety with Psychostimulant Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Anxiety is a commonly reported side-effect of psychostimulant treatment. Our goal was to quantify the risk of anxiety as a side effect of psychostimulant treatment for attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with ADHD. We used a fixed-effects meta-analysis to examine the risk ratio of anxiety reported as a side effect in children treated with psychostimulants compared with those treated with placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dosage, duration of use, and trial design on the measured risk of anxiety. RESULTS: We identified 23 studies involving 2959 children with ADHD for inclusion in our meta-analysis. The risk of anxiety associated with psychostimulant treatment was significantly lower than that experienced with placebo (relative risk [RR] = 0.86 [95% CI: 0.77, 0.95], z = -2.90, p < 0.05). Higher doses of psychostimulants were associated with a reduced measured risk of anxiety of psychostimulants when compared with placebo (ß = -0.0039 [95% CI: -0.00718, -0.00064], z = -2.34, p = 0.019). CONCLUSIONS: Meta-analysis suggests that treatment with psychostimulants significantly reduced the risk of anxiety when compared with placebo. This finding does not rule out the possibility that some children experience increased anxiety when treated with psychostimulants, but suggests that those risks are outweighed by the number of children who experience improvement in anxiety symptoms (possibly as a secondary effect of improved control of ADHD symptoms). Clinicians should consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.

Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials.

OBJECTIVE: Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials. METHOD: We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics. RESULTS: We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials. CONCLUSION: Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.

Meta-analysis: melatonin for the treatment of primary sleep disorders.

STUDY OBJECTIVES: To investigate the efficacy of melatonin compared to placebo in improving sleep parameters in patients with primary sleep disorders. DESIGN: PubMed was searched for randomized, placebo-controlled trials examining the effects of melatonin for the treatment of primary sleep disorders. Primary outcomes examined were improvement in sleep latency, sleep quality and total sleep time. Meta-regression was performed to examine the influence of dose and duration of melatonin on reported efficacy. PARTICIPANTS: Adults and children diagnosed with primary sleep disorders. INTERVENTIONS: Melatonin compared to placebo. RESULTS: Nineteen studies involving 1683 subjects were included in this meta-analysis. Melatonin demonstrated significant efficacy in reducing sleep latency (weighted mean difference (WMD) = 7.06 minutes [95% CI 4.37 to 9.75], Z = 5.15, p<0.001) and increasing total sleep time (WMD = 8.25 minutes [95% CI 1.74 to 14.75], Z = 2.48, p = 0.013). Trials with longer duration and using higher doses of melatonin demonstrated greater effects on decreasing sleep latency and increasing total sleep time. Overall sleep quality was significantly improved in subjects taking melatonin (standardized mean difference = 0.22 [95% CI: 0.12 to 0.32], Z = 4.52, p<0.001) compared to placebo. No significant effects of trial duration and melatonin dose were observed on sleep quality. CONCLUSION: This meta-analysis demonstrates that melatonin decreases sleep onset latency, increases total sleep time and improves overall sleep quality. The effects of melatonin on sleep are modest but do not appear to dissipate with continued melatonin use. Although the absolute benefit of melatonin compared to placebo is smaller than other pharmacological treatments for insomnia, melatonin may have a role in the treatment of insomnia given its relatively benign side-effect profile compared to these agents.