A double-blind switch study of paroxetine and venlafaxine in obsessive-compulsive disorder

BACKGROUND: The treatment guidelines for obsessive-compulsive disorder (OCD) propose to switch serotonin reuptake inhibitors (SRIs) in case of refractoriness. However, no controlled research has been published yet that prospectively examined the effects of changing SRIs. This article describes the first double-blind switch study of 2 SRIs in patients with OCD. METHOD: 150 patients with primary OCD, according to DSM-IV criteria, were randomly assigned in a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine (N = 75) or 60 mg/day of paroxetine (N = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and nonresponse was defined as less than 25% reduction on the Y-BOCS. After a 4-week tapering phase, 43 nonresponders were switched to 12 additional weeks of the alternate antidepressant, of which 16 patients received venlafaxine and 27 received paroxetine. RESULTS: Eighteen of 43 patients benefited from a switch to the alternate SRI with a mean +/- SD decrease of at least 25% on the Y-BOCS. At the end of 12 weeks, responder rates were 56% for paroxetine (15/27) and 19% for venlafaxine (3/16). An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 1.8 +/- 3.5 in the venlafaxine group and 6.5 +/- 7.1 in the paroxetine group. After 2 consecutive SRI trials, 109 of 150 patients (73%) achieved a Y-BOCS decrease of at least 25%. CONCLUSION: The results of the current study show that 42% of the nonresponders benefited from a crossover to the other SRI, and that paroxetine was more efficacious than venlafaxine in the treatment of nonresponders to a previous SRI trial. Switching SRIs in case of refractoriness may be considered a useful strategy for patients with OCD.     

The effect of nitrostyrene on cell proliferation and macrophage immune responses

The use of mood enhancing drugs such as amphetamine and ecstasy are now prevalent in society. These compounds are known to produce serious psychological and physiological problems in users, which can, in some circumstances result in death. While there has been much research into the effects of these drugs on the body, little if any research has investigated the effect of the side products and synthetic reaction by-products which are a consequence of there illegal production. In the study the effects of nitrostyrene, a reaction by-product in one of the routes to synthesis of amphetamine sulphate, on cell viability and macrophage function was determined. Treatment with nitrostyrene at doses >0.75 microg/mL had a significant suppressive effect on the proliferation of stomach cancer lines. Treatment of macrophages with doses as high as 10 microg/mL did not effect cell viability. Nitrostyrene treatment of macrophages, stimulated with IFN gamma and LPS, resulted in a dose dependent differential inhibition in IL12, IL6 and nitrite production, even using doses < 0.5 microg/mL. Thus ranking of the three, on the basis of the suppressive effect obtained, is IL12 > nitrite > IL6. Thus ingestion of nitrostyrene contaminated ecstasy is likely to have a adverse effect on the immune responses of the recreational user.     

A double blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder

SUMMARY: While the usefulness of clomipramine and selective serotonin reuptake inhibitors (SSRIs) in obsessive-compulsive disorder (OCD) has been established, the efficacy of serotonin-norepinephrine reuptake inhibitors remains to be determined. This report describes the first randomized double-blind comparison study of an SNRI in patients with obsessive-compulsive disorder. The current study compares the efficacy and tolerability of venlafaxine with paroxetine. One hundred and fifty patients with primary OCD according to DSM-IV criteria were randomly assigned in a 12-week double-blind trial to receive dosages titrated upward to 300 mg/d of venlafaxine (n = 75) or 60 mg/d of paroxetine (n = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive-compulsive scale (Y-BOCS). Other assessments throughout the trial included the Hamilton depression rating scale, and the Hamilton anxiety rating scale. An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 7.2 +/- 7.5 in the venlafaxine group and of 7.8 +/- 5.4 in the paroxetine group. In both treatment groups, a responder rate (decrease > 35% on the Y-BOCS) of approximately 40% was found. There were no significant differences between venlafaxine and paroxetine with regard to response or responder rates. The incidence of adverse events for venlafaxine and paroxetine was comparable. The most common side effects for venlafaxine were somnolence, insomnia, a dry mouth, and sweating; and for paroxetine somnolence, sweating, nausea, and headache. These results show that venlafaxine was equally effective to paroxetine in treating patients with OCD. Venlafaxine may be a useful therapy for obsessive-compulsive patients, but is not superior to SSRIs.     

1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study

Background

There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma?>?1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma?>?1 mm in BT.

Methods

This phase III, multicentre trial [NCT02385214] administered by the Australia & New Zealand Medical Trials Group (ANZMTG 03.12) randomised patients with a primary cutaneous melanoma?>?1 mm in BT to a 1 versus 2-cm wide excision margin to be performed with sentinel lymph node biopsy. Surgical closure technique was at the discretion of the treating surgeon. Patients’ QoL was measured (FACT-M questionnaire) at baseline, 3, 6, and 12 months after randomisation.

Results

Between January 2015 and June 2016, 400 patients were randomised from 17 centres in 5 countries. A total of 377 patients were available for analysis. Primary melanomas were located on the trunk (56.9%), extremities (35.6%), and head and neck (7.4%). More patients in the 2-cm margin group required reconstruction (34.9 vs. 13.6%; p?<?0.0001). There was an increased wound necrosis rate in the 2-cm arm (0.5 vs. 3.6%; p?=?0.036). After 12 months’ follow-up, no differences were noted in QoL between groups.

Discussion

This pilot study demonstrates the feasibility of a large international RCT to provide a definitive answer to the optimal excision margin for patients with intermediate- to high-risk primary cutaneous melanoma.

     

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct‐disordered juvenile offenders

Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit‐level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct‐disordered juveniles with a history of serious delinquency (N = 50, mean age = 16.83 ± 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait‐specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self‐centered, emotionally cold, and behaviorally disinhibited profile. Hum Brain Mapp 37:4017–4033, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19

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Mechanical properties of achilles tendon in rats induced to experimental diabetes

The aim of this study was to quantify the effect of chemically induced diabetes mellitus (DM) on the mechanical properties of the Achilles tendon of rats and correlate it with metabolic and biomechanical findings. Adult rats were selected randomly and assigned to two groups, the diabetic group consisted of animals receiving a dose of streptozotocin to induce type I diabetes and the control group. The animals were placed in metabolic cages for analysis of metabolism. Ten weeks after diabetes induction, the Achilles tendon of both groups were collected and submitted to a traction test in a conventional testing machine. The measurements of mechanical properties indicated that the elastic modulus (MPa) was significantly higher in the control group (p < 0.01). In Maximum tension (MPa), the groups did not have differences (p > 0.01). Energy/tendon area (N mm/mm²), specific strain (%) and maximum specific strain (mm) were higher in tendon tests of the diabetic group (p < 0.01). We observed that the mechanical properties of tendons have correlations with metabolic properties of the diabetic animals. These results showed that induced DM in rats have an important negative effect on the mechanical properties of the Achilles tendon.     

A systematic review of serologic tests in the diagnosis of necrotizing enterocolitis

Background

Although many serologic markers have been suggested for diagnosis of necrotizing enterocolitis, there is little consensus on which of these is potentially clinically useful. Our aims were (i) to systematically review circulating markers that are potentially useful in the diagnosis of NEC and (ii) to compare the relative performance of each serologic marker of NEC by pooling estimates of marker accuracies and presenting their combined diagnostic accuracies.

Methods

We undertook a systematic review of the literature to identify studies that reported serologic markers at the time of diagnosis of necrotizing enterocolitis. Where possible, we constructed 2-by-2 tables of diagnostic accuracy from each article, if 2 or more studies investigated the same test, their results were meta-analyzed by pooling estimates of sensitivity, specificity, likelihood ratio for positive index test (LR+), likelihood ratio for negative index test (LR−), diagnostic odds ratio, and their corresponding 95% confidence intervals.

Results

Twenty-five articles provided information on serology at the time of diagnosis of necrotizing enterocolitis. Of these, it was possible to construct diagnostic accuracy tables from 16 articles and to combine data from studies that used C-reactive protein, intestinal fatty acid binding protein, and platelet-activating factor. Of these C-reactive protein was a sensitive but nonspecific marker for necrotizing enterocolitis, whereas platelet-activating factor and intestinal fatty acid binding protein were both sensitive and specific.

Conclusions

Most serologic markers of necrotizing enterocolitis have been used in too few studies to evaluate their use. Of those tests that have been tested repeatedly, platelet-activating factor and intestinal fatty acid binding protein are potentially useful, although their use must be further tested in larger prospective studies.     

Lactase persistence-related genetic variant: population substructure and health outcomes

Lactase persistence is an autosomal-dominant trait that is common in European-derived populations. A basic tendency for lactase persistence to increase from the southeast to the northwest across European populations has been noted, but such trends within countries have not been extensively studied. We genotyped the C/T(-13910) variant (rs4988235) that constitutes the putatively causal allele for lactase persistence (T allele representing persistence) in a general population sample of 3344 women aged 60-79 years from 23 towns across Britain. We found an overall frequency of 0.253 for the C (lactase non-persistence) allele, but with considerable gradients of decreasing frequency from the south to the north and from the east to the west of Britain for this allele. Daily sunlight was positively related to C (non-persistence) allele prevalence. However, sunlight exposure and latitude are strongly correlated, and it was not possible to identify which is the primary factor statistically underlying the distribution of lactase persistence. The C/T(-13910) variant (rs4988235) was not related to drinking milk or bone health (although drinking milk itself was protective of bone health), and was essentially unrelated to a wide range of other lifestyle, health and demographic characteristics. One exception was general health being rated as being poor or fair, for which there was an odds ratio of 1.38 (1.04, 1.84) for women homozygous for the C allele; on adjustment for latitude and longitude of place of birth, this attenuated to 1.19 (0.87, 1.64). The lactase persistence variant could contribute to the examination of data for the existence of, and then statistical control for, population substructure in genetic association studies.