Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2-3 months lag time before ...clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid anti-obsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n=15) with near-constant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine's effects within the crossover design showed significant (p<0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n=8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n=7). One-week post-infusion, 50% of those receiving ketamine (n=8) met criteria for treatment response (≥35% Y-BOCS reduction) vs 0% of those receiving placebo (n=7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.
Context: Reduced cortisol levels have been linked with vulnerability to posttraumatic stress disorder (PTSD) and the risk factor of parental PTSD in adult offspring of Holocaust survivors.
Objective: ...The purpose of this study was to report on the relationship between maternal PTSD symptoms and salivary cortisol levels in infants of mothers directly exposed to the World Trade Center collapse on September 11, 2001 during pregnancy.
Design: Mothers (n = 38) collected salivary cortisol samples from themselves and their 1-yr-old babies at awakening and at bedtime.
Results: Lower cortisol levels were observed in both mothers (F = 5.15, df = 1, 34; P = 0.030) and babies of mothers (F = 8.0, df = 1, 29; P = 0.008) who developed PTSD in response to September 11 compared with mothers who did not develop PTSD and their babies. Lower cortisol levels were most apparent in babies born to mothers with PTSD exposed in their third trimesters.
Conclusions: The data suggest that effects of maternal PTSD related to cortisol can be observed very early in the life of the offspring and underscore the relevance of in utero contributors to putative biological risk for PTSD.
The Heineke-Mikulicz and Finney techniques are conventional strictureplasties that have been used to manage short (<10 cm) and medium-length (>10 cm and <20 cm) strictures from Crohn's disease. ...Nonconventional strictureplasty techniques have emerged to facilitate bowel conservation for atypical strictures. These techniques include the modified Finney, combined Heineke-Mikulicz and Finney, modified Heineke-Mikuliczs, Michelassi, and modifications of it and others.
The aim of this study is to compare conventional vs nonconventional strictureplasties with respect to short-term complications and long-term results.
A MEDLINE search was performed using "Crohn's disease", "surgical therapy", "strictureplasty", "complications", "reoperation", and "recurrence" as medical subject headings. Studies conducted between 1975 and June 31, 2010 were found via PubMed, Ovid, Embase, and Cochrane databases and categorized into 3 groups. These groups consist of centers performing conventional strictureplasties, nonconventional strictureplasties, or both. Studies with at least 3 patients were reviewed.
A mixed-effects meta-analysis for each outcome was performed by use of Supermix software by SSI Scientific Software International.
We focused on immediate and long-term complication rates among the groups. The 6 immediate complications include small-bowel obstructions, sepsis, other infections, reoperations, early postoperative GI bleeds, and other early complications. The 5 long-term complications include recurrent strictures, small-bowel obstructions, reoperations, carcinoma, and deaths.
We reviewed 32 studies with 1616 patients who underwent 4538 strictureplasties. One thousand one hundred fifty-seven patients underwent conventional strictureplasties with an early complication rate of 15%; 459 patients underwent nonconventional strictureplasties with an early complication rate of 8%. A late complication rate of 29% for the conventional strictureplasty group and 17% for the nonconventional strictureplasty group was noted.
We are limited by the data published with the inherent risk of finding and analyzing mostly articles with positive results.
The nonconventional strictureplasty techniques were noninferior to the conventional strictureplasty procedures with respect to all prespecified outcomes.
In 2003 and 2004, U.S. and European regulators issued public health warnings about a possible association between antidepressants and suicidal thinking and behavior. The authors assessed whether ...these warnings discouraged use of antidepressants in children and adolescents and whether they led to increases in suicide rates as a result of untreated depression.
The authors examined U.S. and Dutch data on prescription rates for selective serotonin reuptake inhibitors (SSRIs) from 2003 to 2005 in children and adolescents (patients up to age 19), as well as suicide rates for children and adolescents, using available data (through 2004 in the United States and through 2005 in the Netherlands). They used Poisson regression analyses to determine the overall association between antidepressant prescription rates and suicide rates, adjusted for sex and age, during the periods preceding and immediately following the public health warnings.
SSRI prescriptions for youths decreased by approximately 22% in both the United States and the Netherlands after the warnings were issued. In the Netherlands, the youth suicide rate increased by 49% between 2003 and 2005 and shows a significant inverse association with SSRI prescriptions. In the United States, youth suicide rates increased by 14% between 2003 and 2004, which is the largest year-to-year change in suicide rates in this population since the Centers for Disease Control and Prevention began systematically collecting suicide data in 1979.
In both the United States and the Netherlands, SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents.
Obsessive-compulsive disorder (OCD) is one of the world's most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved ...by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP).
To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD.
A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial.
While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks.
The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity.
Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean SE, -9.72 1.38; P < .001 vs placebo: mean SE, -10.10 1.68; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean SE, -0.38 1.72; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life.
Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile.
clinicaltrials.gov Identifier: NCT00389493.
Little is known about influences of sample selection on estimation in propensity score matching. The purpose of the study was to assess potential selection bias using one-to-one greedy matching ...versus optimal full matching as part of an evaluation of supportive housing in New York City (NYC).
Data came from administrative data for 2 groups of applicants who were eligible for an NYC supportive housing program in 2007-09, including chronically homeless adults with a substance use disorder and young adults aging out of foster care. We evaluated the 2 matching methods in their ability to balance covariates and represent the original population, and in how those methods affected outcomes related to Medicaid expenditures.
In the population with a substance use disorder, only optimal full matching performed well in balancing covariates, whereas both methods created representative populations. In the young adult population, both methods balanced covariates effectively, but only optimal full matching created representative populations. In the young adult population, the impact of the program on Medicaid expenditures was attenuated when one-to-one greedy matching was used, compared with optimal full matching.
Given covariate balancing with both methods, attenuated program impacts in the young adult population indicated that one-to-one greedy matching introduced selection bias.
Objective: To determine long-term effects on substance use and substance use disorder (SUD), up to 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the multisite ...Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA; n = 436); to test whether medication at follow-up, cumulative psychostimulant treatment over time, or both relate to substance use/SUD; and to compare substance use/SUD in the ADHD sample to the non-ADHD childhood classmate comparison group (n = 261). Method: Mixed-effects regression models with planned contrasts were used for all tests except the important cumulative stimulant treatment question, for which propensity score matching analysis was used. Results: The originally randomized treatment groups did not differ significantly on substance use/SUD by the 8-year follow-up or earlier (mean age = 17 years). Neither medication at follow-up (mostly stimulants) nor cumulative stimulant treatment was associated with adolescent substance use/SUD. Substance use at all time points, including use of two or more substances and SUD, were each greater in the ADHD than in the non-ADHD samples, regardless of sex. Conclusions: Medication for ADHD did not protect from, or contribute to, visible risk of substance use or SUD by adolescence, whether analyzed as randomized treatment assignment in childhood, as medication at follow-up, or as cumulative stimulant treatment over an 8-year follow-up from childhood. These results suggest the need to identify alternative or adjunctive adolescent-focused approaches to substance abuse prevention and treatment for boys and girls with ADHD, especially given their increased risk for use and abuse of multiple substances that is not improved with stimulant medication. Clinical trial registration information--Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); http://clinical trials.gov/; NCT00000388. (Contains 2 figures and 1 table.)
The mechanisms underpinning plant perception of phloem-feeding insects, particularly aphids, remain poorly characterized. Therefore, the role of apoplastic redox state in controlling aphid ...infestation was explored using transgenic tobacco (Nicotiana tabacum) plants that have either high (PAO) or low (TAO) ascorbate oxidase (AO) activities relative to the wild type. Only a small number of leaf transcripts and metabolites were changed in response to genotype, and cell wall composition was largely unaffected. Aphid fecundity was decreased significantly in TAO plants compared with other lines. Leaf sugar levels were increased and maximum extractable AO activities were decreased in response to aphids in all genotypes. Transcripts encoding the Respiratory Burst Oxidase Homolog F, signaling components involved in ethylene and other hormone-mediated pathways, photosynthetic electron transport components, sugar, amino acid, and cell wall metabolism, were increased significantly in the TAO plants in response to aphid perception relative to other lines. The levels of galactosylated xyloglucan were decreased significantly in response to aphid feeding in all the lines, the effect being the least in the TAO plants. Similarly, all lines exhibited increases in tightly bound (1→4)-𝛽-galactan. Taken together, these findings identify AO-dependent mechanisms that limit aphid infestation.
In late 2006, a U.S. Food and Drug Administration advisory committee recommended that the 2004 black box warning regarding suicidality in pediatric patients receiving antidepressants be extended to ...include young adults. This study examined the relationship between antidepressant treatment and suicide attempts in adult patients in the Veterans Administration health care system.
The authors analyzed data on 226,866 veterans who received a diagnosis of depression in 2003 or 2004, had at least 6 months of follow-up, and had no history of depression from 2000 to 2002. Suicide attempt rates overall as well as before and after initiation of antidepressant therapy were compared for patients who received selective serotonin reuptake inhibitors (SSRIs), new-generation non-serotonergic-specific (non-SSRI) antidepressants (bupropion, mirtazapine, nefazodone, and venlafaxine), tricyclic antidepressants, or no antidepressant. Age group analyses were also performed.
Suicide attempt rates were lower among patients who were treated with antidepressants than among those who were not, with a statistically significant odds ratio for SSRIs and tricyclics. For SSRIs versus no antidepressant, this effect was significant in all adult age groups. Suicide attempt rates were also higher prior to treatment than after the start of treatment, with a significant relative risk for SSRIs and for non-SSRIs. For SSRIs, this effect was seen in all adult age groups and was significant in all but the 18-25 group.
These findings suggest that SSRI treatment has a protective effect in all adult age groups. They do not support the hypothesis that SSRI treatment places patients at greater risk of suicide.
PDF
