Abstract Glutamatergic N-methyl- d -aspartate (NMDA) receptor hypofunction has been proposed as a mechanism underlying psychosis. d -cycloserine, a partial agonist at the glycine site of the NMDA ...receptor, enhances learning in animal models, although tachyphylaxis develops with repeated dosing. Once-weekly dosing of d -cycloserine produces persistent improvement when combined with cognitive behavioral therapy (CBT) in anxiety disorders. Delusional beliefs can be conceptualized as a learning deficit, characterized by the failure to use contradictory evidence to modify the belief. CBT techniques have been developed with modest success to facilitate such reality-testing (or new learning) in delusional beliefs. The current study evaluated whether d -cycloserine could potentiate beneficial effects of CBT on delusional severity. Twenty-one outpatients with schizophrenia or schizoaffective disorder and moderately severe delusions were randomized in a double-blind cross-over design to receive a single-dose of either d -cycloserine 50 mg or placebo in a counterbalanced order on two consecutive weeks 1 h prior to a CBT intervention involving training in the generation of alternative beliefs. Assessments were completed at baseline, 7 days following the first study drug administration and 7 days following the second study drug administration. Contrary to prediction, there was no significant d -cycloserine treatment effect on delusional distress or severity as measured by the SAPS or PSYRATS. An unexpected finding was an order effect, whereby subjects who received d -cycloserine first had significantly reduced delusional severity, distress, and belief conviction on PSYRATS compared to subjects who received placebo first. However, this finding is consistent with animal models in which d -cycloserine enhances learning only when accompanying the first exposure to training.
Etanercept: An overview Goffe, Ben; Cather, Jennifer Clay
Journal of the American Academy of Dermatology,
08/2003, Letnik:
49, Številka:
2
Journal Article
Recenzirano
Etanercept, a competitive inhibitor of TNF-α, is currently FDA approved for psoriatic arthritis and rheumatoid arthritis. The molecular structure of etanercept, its mechanism of action, and results ...of clinical trials involving patients with psoriasis will be reviewed.
Substance use disorders have a profound impact on the course of severe mental illnesses and on the family, but little research has evaluated the impact of family intervention for this population. To ...address this question, a randomized controlled trial was conducted comparing a brief (2-3 mo) Family Education (ED) program with a longer-term (9-18 mo) program that combined education with teaching communication and problem-solving skills, Family Intervention for Dual Disorders (FIDD). A total of 108 clients (77% schizophrenia-spectrum) and a key relative were randomized to either ED or FIDD and assessed at baseline and every 6 months for 3 years. Rates of retention of families in both programs were moderate. Intent-to-treat analyses indicated that clients in both programs improved in psychiatric, substance abuse, and functional outcomes, as did key relatives in knowledge of co-occurring disorders, burden, and mental health functioning. Clients in FIDD had significantly less severe overall psychiatric symptoms and psychotic symptoms and tended to improve more in functioning. Relatives in FIDD improved more in mental health functioning and knowledge of co-occurring disorders. There were no consistent differences between the programs in substance abuse severity or family burden. The findings support the utility of family intervention for co-occurring disorders, and the added benefits of communication and problem-solving training, but also suggest the need to modify these programs to retain more families in treatment in order to provide them with the information and skills they need to overcome the effects of these disorders.
Atopic dermatitis (AD) is a chronic pruritic skin disease that can have a profound negative impact on patients’ quality of life, especially in cases of inadequate disease control. Dupilumab, a dual ...inhibitor of IL-4 and IL-13 signaling, is approved in the United States for the treatment of moderate-to-severe AD in adults (≥ 18 years old) and in children (≥ 6 years old). In this review, we present results from phase 3 trials evaluating dupilumab’s efficacy and safety in adults, adolescents, and children. These trials demonstrate that dupilumab provides rapid improvements (in as little as 1 week) and sustained efficacy (up to 4 years) when used as a treatment for moderate-to-severe AD. Dupilumab not only improves skin signs and symptoms, but also provides multiple health benefits beyond the skin, including improvements in quality of life, itch, sleep disturbances, and pain/discomfort. Dupilumab is generally well tolerated, has a favorable safety profile in adults, adolescents, and children, has no serious drug–drug interactions, does not require routine laboratory testing, and is not an immunosuppressant. Taken together, phase 3 trials demonstrate that dupilumab provides rapid and sustained efficacy and is generally well tolerated for the treatment of moderate-to-severe AD across age groups.
An improved understanding regarding the pathophysiology of psoriasis, coupled with advances in molecular research, has prompted the development of targeted biologic treatments for patients with ...plaque psoriasis. T lymphocytes play an important role in initiating the immune system and the inflammatory responses that result in the development and maintenance of psoriatic plaques. Efalizumab (anti-CD11a, Raptiva™; Genentech, Inc.) is a mAb that targets the T cell adhesion molecule, leukocyte function-associated antigen-1 (LFA-1). By binding to CD11a - the α-subunit of LFA-1 - LFA-1 is prevented from binding with its ligand, intercellular adhesion molecule-1 (ICAM-1). This inhibits various T cell processes believed to be important in the pathogenesis of psoriasis, including T cell activation, T cell adhesion to endothelial cells and T cell migration. Clinical trials demonstrate that efalizumab, given subcutaneously once-weekly, provides clinical benefit, including improved quality of life, in patients with moderate-to-severe plaque psoriasis. Efalizumab is associated with an early onset of action, with improvement noted as early as 14 days. Studies with extended treatment suggest that continuing efalizumab therapy is more beneficial in maintaining and improving responses. Relapse of psoriasis is usually seen within 60 - 70 days after discontinuation of therapy, and rebound in ~ 5% of patients (i.e., flare to > 125% of baseline) is noted. Efalizumab is associated with acute adverse events during the first and second injections, which decrease in incidence with each subsequent injection. Data indicate that efalizumab can be safely administered for extended periods of time. Given the efficacy, early onset of clinical benefit, the safety profile and the convenience of once-weekly subcutaneous home dosing, efalizumab offers an interesting new therapeutic option for the treatment of psoriasis and the potential for improved and potentially safer long-term, continuous 'maintenance' therapy.
Forty-two patients with cutaneous T-cell lymphoma, including 31 with exfoliative erythroderma or Sezary syndrome and 11 with mycosis fungoides, were studied for the occurrence of staphylococcal ...infection. Thirty-two of 42 (76%) had a positive staphylococcal culture from skin or blood. One half of the patients with positive cultures grew Staphylococcus aureus. This group included 11 with Sezary syndrome and 5 with rapidly enlarging mycosis fungoides plaques or tumors. All of the S aureus carried enterotoxin genes. Surprisingly, 6 of 16 strains were the same toxic shock toxin-1 (TSST-1)-positive clone, designated electrophoretic type (ET)-41. Analysis of the T-cell receptor Vβ repertoire in 14 CTCL patients found that only 4 had the expected monoclonal expansion of a specific Vβ gene, whereas 10 had oligoclonal or polyclonal expansion of several Vβ families. All patients with TSST-1+S aureus had overexpansion of Vβ 2 in blood and/or skin lesions. These studies show that S aureus containing superantigen enterotoxins are commonly found in patients with CTCL, especially individuals with erythroderma where they could exacerbate and/or perpetuate stimulate chronic T-cell expansion and cutaneous inflammation. Attention to toxigenic S aureus in CTCL patients would be expected to improve the quality of care and outcome of this patient population.
Clinical trials for systemic psoriasis therapy typically enroll healthy patients and exclude patients with cardiovascular disease, latent tuberculosis, liver disease, histories of malignancies, viral ...infections, children, and pregnant or breast-feeding women. Physicians often require guidance for optimum management of severe psoriasis in patients that have a combination of underlying disease states. To provide treatment recommendations for complex psoriasis scenarios, a consensus panel comprising 15 experts in psoriatic disease convened to review and discuss available evidence-based data and to arrive at a consensus for treatment options of difficult cases. An application of the Delphi Method was used to select case scenarios, provide medical treatment options, present the case study with existing medical evidence, and anonymously vote on treatment options. The top 10 treatment options were ranked and statistically analyzed to compare the differences between treatments. The final rankings and analysis provide guidance for practical, safe, and efficacious treatment options in a number of complex psoriasis scenarios.
Efalizumab is a humanised monoclonal antibody targeting the CD11a subunit of lymphocyte function-associated antigen-1, specifically developed for ps-oriasis. Indicated for patients with ...moderate-to-severe plaque psoriasis, efalizumab is FDA-approved in the US for patients aged ≥ 18, as well as being approved in several other European countries. Clinical studies have proven the efficacy of efalizumab for a majority of patients, improving quality of life with continuous maintenance therapy by means of weekly subcutaneous self-injections. Controlled trials have demonstrated the safety and tolerability of efalizumab. Clinical trials have established that ~ 30% of patients can achieve a PASI-75 response within 12weeks of initiating treatment, with further clinical benefit noted with continued therapy up to 24 and even 36months of therapy. Efalizumab may thus potentially offer patients a safe option for long-term safe control in managing their disease.
The use of botulinum toxin has revolutionized the treatment of facial lines with an incomparable safety record over the past 14 years. The most common used injection sites are shown in Fig. 9. With ...the recent FDA approval for Botox in the treatment of glabellar lines, its use will likely increase dramatically. It is essential that practitioners have a detailed and specific knowledge of the facial and neck musculature to be injected to minimize untoward side effects, especially in the early days of new users' learning curve. The specifics of the dilutions and units per amount used for the various different commercial forms of botulinum toxin types A and B need to be understood fully and standardized together with the potential for antigenicity with the higher protein load of type B. In addition, specific indications for the use of botulinum toxin as adjunctive therapy for specific facial surgical procedures (i.e., blepharoplasty, surgical brow lift, and laser resurfacing) will become better understood. figure: see text Finally, even though the anatomy of the facial musculature is well described, individual differences in men and women, in different population groups, and in tissue qualities, such as turgor and elasticity 87, are important factors to be considered before undertaking botulinum toxin injections. It is likely that the use of specific measuring devices, such as digital imaging, will further help define the use of botulinum toxin for different muscle groups and facial aesthetic indications.
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