Effectiveness of the Dexamethasone Intravitreal Implant for Treatment of Patients with Diabetic Macular Oedema

Diabetic macular oedema (DMO) is a leading cause of vision loss in the working-age population worldwide. Corticosteroid drugs have been demonstrated to inhibit the expression of both the vascular endothelial growth factor (VEGF) gene and other anti-inflammatory mediators, such as prostaglandins. Triamcinolone, fluocinolone and dexamethasone are the main steroids that have been studied for the treatment of macular oedema. Over the last few years, several studies have suggested an important role for dexamethasone in the management of DMO. The dexamethasone intravitreal implant (DEX implant) (Ozurdex®; Allergan, Inc., Irvine, CA) is a novel approach approved by the US Food and Drug Administration (FDA) and by the EU for the intravitreal treatment of macular oedema after branch or central retinal vein occlusion, and for the treatment of non-infectious uveitis affecting the posterior segment of the eye. We reviewed manuscripts that had investigated the pharmacokinetics, efficacy and safety of the DEX implant regarding DMO treatment.

Low Dose Thalidomide for Treatment of Resistant Discoid Lupus Erythematosus. A Case Report

Discoid lupus erythematosus (DLE) is a chronic, indolent, disfiguring disease that is characterized by scaly, erythematous, disk-shaped patches and plaques followed by atrophy, scarring and depigmentation. In a small number of patients, it is refractory to standard therapies. In several studies, thalidomide has been reported to be an effective treatment in those cases. The most fearful side effects are teratogenicity and neuropathy. Adequate counseling and vigilance must be given to the patients. We report a 45-year-old Portuguese woman who presented with a 20-year history of severe facial and scalp DLE confirmed by histopathology. For several years, it failed to respond to several therapies, including topical, intralesional and oral corticosteroids, hydroxychloroquine, methotrexate, azathioprine and topical tacrolimus. Thalidomide was initiated at a dosage of 50mg/day and the skin lesions had improved dramatically after three weeks with complete clinical remission. Two months later, the dose was reduced to 50mg, five days per week without disease rebound. The patient´s concomitant medications during the treatment included sunscreen, hydroxycholoroquine, enoxaparin and aspirin to prevent thromboembolic events. Pregnancy testing, routine laboratory and electrocardiography were performed at regular intervals for safety monitoring and the results were within normal limits. Only minor side effects as nausea, constipation and somnolence were noted, however, they improved with dose reduction. Our data confirm that thalidomide therapy is an alternative or adjunctive treatment for patients with severe, chronic DLE that is refractory to standard therapies. In this patient, low-dose thalidomide was an effective treatment with minimal side effects.

HIV-2 Integrase Polymorphisms and Longitudinal Genotypic Analysis of HIV-2 Infected Patients Failing a Raltegravir-Containing Regimen

To characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naïve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTI-major resistance mutations were detected in the virus population from naïve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.

Neurogenic Thoracic Outlet Syndrome Associated with Cervical Rib

A true neurogenic thoracic outlet syndrome (TOS) associated with a cervical rib is considered extremely rare. The authors present their experience with 5 cases of true neurogenic TOS associated with a cervical rib. All patients were female and had a cervical rib confirmed radiographically pre-operatively. Average age was 34,8 years. Although all patients had been treated with several combinations of diverse drugs and a rehabilitation program before referral to surgery, all described their pain as intense and debilitating before surgical treatment. All patients had pre-operative electromyographic abnormalities. Patients were operated on via a supraclavicular approach and the cervical rib was resected. No intra-operative or postoperative complications were noted. Two years postoperatively, all patients mentioned improvement. However, only 2 were symptomless, and on no medication. In one patient there was significant improvement, and in the remaining 2 patients some residual pain persisted that had to be dealt with pharmacologically. All patients were able to resume their daily life activities. Recovery was poorer in the 2 patients that had been referred to surgery after a longer period of time since the beginning of symptoms.

Economic Evaluation of Ticagrelor for Secondary Prevention Following Acute Coronary Syndromes

INTRODUCTION AND OBJECTIVES: To estimate the cost-effectiveness and cost-utility of ticagrelor in the treatment of patients with acute coronary syndromes (unstable angina or myocardial infarction with or without ST-segment elevation), including patients treated medically and those undergoing percutaneous coronary intervention or coronary artery bypass grafting. METHODS: A short-term decision tree and a long-term Markov model were used to simulate the evolution of patients' life-cycles. Clinical effectiveness data were collected from the PLATO trial and resource use data were obtained from the Hospital de Santa Marta database, disease-related group legislation and the literature. RESULTS: Ticagrelor provides increases of 0.1276 life years and 0.1106 quality-adjusted life years (QALYs) per patient. From a societal perspective these clinical gains entail an increase in expenditure of €610. Thus the incremental cost per life year saved is €4780 and the incremental cost per QALY is €5517. CONCLUSIONS: The simulation results show that ticagrelor reduces events compared to clopidogrel. The costs of ticagrelor are partially offset by lower costs arising from events prevented. The use of ticagrelor in clinical practice is therefore cost-effective compared to generic clopidogrel.

STARTVerso1: A Randomized Trial of Faldaprevir Plus Pegylated Interferon/Ribavirin for Chronic HCV Genotype-1 Infection

BACKGROUND & AIMS: The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection. METHODS: Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p < 0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components. CONCLUSIONS: Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg.