Meta-analysis: hoarding symptoms associated with poor treatment outcome in obsessive-compulsive disorder.

DSM-5 recognizes hoarding disorder as distinct from obsessive-compulsive disorder (OCD), codifying a new consensus. Hoarding disorder was previously classified as a symptom of OCD and patients received treatments designed for OCD. We conducted a meta-analysis to determine whether OCD patients with hoarding symptoms responded differently to traditional OCD treatments compared with OCD patients without hoarding symptoms. An electronic search was conducted for eligible studies in PubMed. A trial was eligible for inclusion if it (1) was a randomized controlled trial, cohort or case-control study; (2) compared treatment response between OCD patients with and those without hoarding symptoms, or examined response to treatment between OCD symptom dimensions (which typically include hoarding) and (3) examined treatment response to pharmacotherapy, behavioral therapy or their combination. Our primary outcome was differential treatment response between OCD patients with and those without hoarding symptoms, expressed as an odds ratio (OR). Twenty-one studies involving 3039 total participants including 304 with hoarding symptoms were included. Patients with OCD and hoarding symptoms were significantly less likely to respond to traditional OCD treatments than OCD patients without hoarding symptoms (OR=0.50 (95% confidence interval 0.42-0.60), z=-7.5, P<0.0001). This finding was consistent across treatment modalities. OCD patients with hoarding symptoms represent a population in need of further treatment research. OCD patients with hoarding symptoms may benefit more from interventions specifically targeting their hoarding symptoms.

Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis.

We conducted a meta-analysis of randomized, placebo-controlled trials of omega-3 fatty acid (FA) treatment of major depressive disorder (MDD) in order to determine efficacy and to examine sources of heterogeneity between trials. PubMed (1965-May 2010) was searched for randomized, placebo-controlled trials of omega-3 FAs for MDD. Our primary outcome measure was standardized mean difference in a clinical measure of depression severity. In stratified meta-analysis, we examined the effects of trial duration, trial methodological quality, baseline depression severity, diagnostic indication, dose of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in omega-3 preparations, and whether omega-3 FA was given as monotherapy or augmentation. In 13 randomized, placebo-controlled trials examining the efficacy of omega-3 FAs involving 731 participants, meta-analysis demonstrated no significant benefit of omega-3 FA treatment compared with placebo (standard mean difference (SMD)=0.11, 95% confidence interval (CI): -0.04, 0.26). Meta-analysis demonstrated significant heterogeneity and publication bias. Nearly all evidence of omega-3 benefit was removed after adjusting for publication bias using the trim-and-fill method (SMD=0.01, 95% CI: -0.13, 0.15). Secondary analyses suggested a trend toward increased efficacy of omega-3 FAs in trials of lower methodological quality, trials of shorter duration, trials which utilized completers rather than intention-to-treat analysis, and trials in which study participants had greater baseline depression severity. Current published trials suggest a small, non-significant benefit of omega-3 FAs for major depression. Nearly all of the treatment efficacy observed in the published literature may be attributable to publication bias.

Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder.

We sought to determine differences in efficacy and tolerability between different doses of selective serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder (OCD) using meta-analysis. We identified 9 studies involving 2268 subjects that were randomized, double-blind placebo-controlled clinical trials that compared multiple, fixed-doses of selective serotonin reuptake inhibitors (SSRIs) to each other and to placebo in the treatment of adults with OCD. Change in Y-BOCS score, proportion of treatment responders, and dropouts (all-cause and due to side-effects) were determined for each included study. Weighted mean difference was used to examine mean change in Y-BOCS score. Pooled absolute risk difference was used to examine dichotomous outcomes. Meta-analysis was performed using a fixed effects model in RevMan 4.2.8. We found that compared with either low or medium doses, higher doses of SSRIs were associated with improved treatment efficacy, using either Y-BOCS score or proportion of treatment responders as an outcome. Dose of SSRIs was not associated with the number of all-cause dropouts. Higher doses of SSRIs were associated with significantly higher proportion of dropouts due to side-effects. These results suggests that higher doses of SSRIs are associated with greater efficacy in the treatment of OCD. This SSRI efficacy pattern stands in contrast to other psychiatric disorders like Major Depressive Disorder. This greater treatment efficacy is somewhat counterbalanced by the greater side-effect burden with higher doses of SSRIs. At present, there are insufficient data to generalize these findings to children or adolescents with OCD.

A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder.

As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.

Circadian patterns of emergency asthma presentations: implications for staffing and treatment.

UNLABELLED: Are there circadian patterns for time of presentation and clinical status in asthmatic patients admitted to an emergency department for acute exacerbations? DESIGN: Prospective observational study. SETTING: Urban community teaching hospital emergency department. PARTICIPANTS: 279 consecutive patients who presented a total of 310 times with asthma exacerbations between October 19 and December 31, 1993. We grouped patients aged 16 years and above as adults and patients younger than 16 years of age as children. INFORMATION COLLECTED: Time of emergency department presentation, time attack began (for adult patients), peak expiratory flowrate prior to emergency department treatment (for adult patients), need for hospital admission, ventilatory failure during an acute attack, and death during an acute attack. RESULTS: Circadian patterns were demonstrated for time of presentation. For the total study group, the peak time of presentation was 8:00 PM to 11:59 PM (p < 0.05) and the trough time of presentation was 4:00 AM to 7:59 AM (p < 0.01). There were differences in peak time of presentation for patients grouped by age. For adult patients only, the peak time of presentation was 8:00 AM to 11:59 AM (p < 0.01), whereas for children only, the peak time of presentation was 8:00 PM to 11:59 PM (p < 0.001). No statistically significant patterns in time of attack onset, hospital admission rates, or peak flow measurements were observed. CONCLUSIONS: There are circadian patterns for the time at which patients with acute asthmatic exacerbations present to our emergency department. Adult patients have a peak time of presentation between 8:00 AM and 11:59 AM, whereas children have an apparent peak time of presentation between 8:00 PM and 11:59 PM. For all age groups, there is a trough in presentation between 4:00 AM and 7:59 AM.

Vitiligo and polyglandular autoimmune endocrinopathy.

Vitiligo is probably an autoimmune disorder of the skin and is commonly associated with a number of known autoimmune endocrinopathies. We present a patient with vitiligo associated with diabetes mellitus and autoimmune thyroid disease. Further, we present evidence that vitiligo and autoimmune disorders coexist and discuss the interrelationship between vitiligo and autoimmune endocrine disorders.

Arachidonic acid metabolic pathway of the rabbit placenta.

Placenta microsomes prepared from animals late in gestation (29 days) efficiently metabolize arachidonic acid into PGE2, PGF2 alpha, PGD2, TxA2 and little or no prostacyclin. In contrast to the late gestation placenta, the early (17 day) placental microsomes synthesize primarily PGE2. The cytosolic (100,000 X g supernatant) fraction from early or late gestation placentae converted arachidonic acid, with a calcium dependent enzyme, into non-polar metabolites whose synthesis was inhibited by ETYA but not indomethacin. These metabolites were purified by HPLC and GC-MS analysis indicated the presence of 12-hydroxy-, 15-hydroxy-, and 11-hydroxy-eicosatetraenoic acid. The mitochondrial (8,000 X g pellet) produced PGE2; PGF2 alpha; 12-, 11-, 15-HETE; the C-17 fragment HHT; and the unusual cyclooxygenase metabolite 15-keto-PGE2. These biologically active metabolites may play a vital role in the reproductive function of the placenta.

Arachidonic acid metabolism by rabbit fetal membranes of various gestational ages.

The ability of rabbit fetal membranes to convert arachidonic acid to both lipoxygenase and cyclooxygenase products was studied by separation and identification of products derived from incubations of 1-14C-arachidonate with subcellular fractions obtained by differential centrifugation of tissue homogenates. Both amnion and splanchnopleure (the chorion-equivalent of the rabbit) produced a mixture of 11-, 12-, and 15-hydroxyeicosatetraenoic acids when stimulated by calcium ions; these products were produced in greater quantity in middle pregnancy (20-22d) than later (28-30d). Cyclooxygenase products included PGD2, PGE2, TxB2 and PGF2 alpha, all of which were made more actively in late pregnancy than the middle in both amnion (which was more active) and chorion-equivalent. These data suggest that arachidonate metabolism by rabbit fetal membranes in middle pregnancy is directed primarily toward production of monohydroxy fatty acids, but that as pregnancy nears term, the PG-producing enzymes are induced, preparing the uterine smooth muscle for parturition.

Prostaglandin production by the pregnant and non-pregnant rabbit uterus.

We have studied the prostaglandin synthesis of the pregnant and non-pregnant rabbit uterus in a microsomal membrane preparation, and in an ex vivo perfused uterus preparation which retains agonist stimulated prostaglandin production. In both the microsomal and isolated perfused system, prostacyclin was the major arachidonic acid metabolite produced; PGE2 was also produced in substantial quantities while TxB2 and PGF2 alpha were not detectable. Moreover, oxytocin was a specific stimulus of PGE2 release. The steroid hormone milieu influenced the level of agonist stimulated prostaglandin release; in general, ovariectomized, estrogen treated animals were more responsive to agonist stimulation than those treated with estrogen followed by progesterone. The microsomal studies indicated that the pregnant animal had a greatly enhanced capacity to metabolize arachidonic acid when compared with the non-pregnant animal. However, this was not reflected in the ability of agonists to stimulate prostaglandin release in the ex vivo perfused preparation.