A Placebo-Controlled Trial of Dextromethorphan as an Adjunct in Opioid-Dependent Patients Undergoing Methadone Maintenance Treatment

Background:

Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT).

Methods:

Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor–β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect.

Results:

After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different.

Conclusions:

We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT.     

Disproportionate Reduction of Serotonin Transporter May Predict the Response and Adherence to Antidepressants in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM

Background:

Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants.

Methods:

We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[¹⁸F]fluorophenylthio)benzylamine (4-[¹⁸F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more.

Results:

Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders.

Conclusions:

The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD.     

Pulmonary complications in bone marrow transplantation: a practical approach to diagnosis and treatment

Pulmonary complications occur in 40% to 60% of recipients of bone marrow trans-plants, account for more than 90% of mortality, and develop during identifiable phases. Phase 1 (Days 1-30) includes pulmonary edema; diffuse alveolar hemorrhage; and various bacterial, fungal, and viral infections; Phase 2 (Days 31-100) usually requires a distinction between cytomegalovirus pneumonitis and idiopathic pneumonia syndrome; and Phase 3 (Day 100+) includes complications that are due to chronic graft-versus-host disease and associated bronchiolitis obliterans. The spectrum of pulmonary complications has been influenced by changes in transplantation technique, prophylactic treatment for infections, and the use of new chemotherapeutic agents that contribute to lung injury. Nonetheless, infections remain a leading cause of morbidity and mortality. The most serious complications result in respiratory failure, for which the prognosis has not improved significantly over the last 2 decades. In this article, we describe our algorithmic approach to the diagnosis and management of these complications.     

A practical approach to reporting treatment abandonment in pediatric chronic conditions

Treatment abandonment, the failure to complete therapy that is required for definitive disease control, frequently causes treatment failure for pediatric patients in low‐ and middle‐income countries with chronic conditions, particularly cancer. Other forms of incomplete treatment affecting children in all settings, such as nonadherence and loss to follow‐up, are often confused with treatment abandonment. Unclear definitions of incomplete treatment dramatically affect reported outcomes. To facilitate disease‐specific and cross‐sector analyses, we outline a practical approach to categorize forms of incomplete treatment, present distinct semantic categories with case examples and provide an algorithm that could be tailored to disease‐ and context‐specific needs. Pediatr Blood Cancer 2015;62:565–570. © 2015 Wiley Periodicals, Inc.     

Lower risk of primary Sjogren’s syndrome in patients with dengue virus infection: a nationwide cohort study in Taiwan

Clinical Rheumatology - The data concerning the association between dengue viruses (DV) infection and autoimmune diseases (ADs) remain unclear and are scarce. This nationwide population-based...     

The effect of fluvastatin on fibrinolytic factors in patients with hypercholesterolemia

Several studies have shown cardiovascular benefit in treating hypercholesterolemia with HMG-CoA reductase inhibitor. However, in addition to the lowering of cholesterol, the beneficial effects of this inhibitor reflect other pharmacological activities. Whether these beneficial effects are partly mediated by changes in fibrinolytic factors remains to be proven, since clinical studies on the effects of HMG-CoA reductase inhibitors on fibrinolytic factors have not yielded consistent results. The purpose of this study was to evaluate the effects of fluvastatin on fibrinolytic factors in hypercholesterolemic patients. After 6 weeks on a low-fat, low-cholesterol diet, 23 outpatients known to have primary hypercholesterolemia with low density lipoprotein cholesterol (LDL-C) > or = 130 mg/dl with at least 2 risk factors or fasting LDL-C > or = 160 mg/dl were selected for the study. Venous blood samples were collected at baseline and at 8 weeks after fluvastatin therapy (40 mg/day) to measure of tissue plasminogen activator (t-PA), plasminogen activators inhibitor-1 (PAI-1), fibrinogen, D-dimer and lipid profile. After 8 weeks of therapy, fluvastatin reduced serum cholesterol by 11% (261.9 mg/dl vs 233.2 mg/dl, P < 0.01) and LDL-C by 22% (191.9 mg/dl vs 149.3 mg/dl, P < 0.01). D-dimer was significantly decreased (0.38 ng/L vs 0.28 ng/L, P = 0.02) and tPA, PAI-1 and fibrinogen tended to decrease after therapy. Fluvastatin therapy improved fibrinolytic profile; the result of this study may in part explain the benefit of HMG-CoA reductase inhibitor on cardiovascular system other than lipid lowering.     

Anatomic problems associated with arterial switch procedures for double outlet right ventricle with subpulmonary ventricular septal defect

Two cases of double outlet right ventricle with subpulmonary ventricular septal defect treated by arterial switch operations are reported. The anatomical problems of coronary artery transfer, occult outflow tract obstruction and position of the pulmonary bifurcation are discussed. Cases of double outlet right ventricle and subpulmonary ventricular septal defect with anterior-to-posterior relation of the great arteries are suited to the repair techniques pioneered by Jatene for complete transposition and ventricular septal defect. Cases in which the great arteries are side-by-side pose more difficult problems, partly because of the more complex and varied anatomy of the coronary arteries, and because of the spatial relation of the roots of the great arteries. Although it may be possible to overcome these technical problems, we have reservations about the reproducibility of such a procedure. We believe, however, that cases of this type are best treated without recourse to "inflow" correction. The options are either the arterial switch procedure or a modified Rastelli operation.