Introduction: Current guidelines recommend an initial pleural aspiration in the investigation and management of suspected malignant pleural effusions (MPEs) with the aim of establishing a diagnosis, identifying non-expansile lung (NEL) and, at times, providing a therapeutic procedure. A wealth of research has been published since the guidelines suggesting that results and outcomes from an aspiration may not always provide sufficient information to guide management. It is important to establish the validity of these findings in a 'real world' population.
View Article and Find Full Text PDFPegvaliase is an enzyme substitution therapy developed to lower blood phenylalanine (Phe) in adults with phenylketonuria (PKU). In phase 3 clinical studies, pegvaliase substantially reduced mean blood Phe in adult subjects with PKU. The most common type of adverse event observed in the pegvaliase clinical program was hypersensitivity adverse events (HAEs), which included occurrences of arthralgia, rash, and pruritis.
View Article and Find Full Text PDFBackground: This study assessed the immunogenicity of pegvaliase (recombinant Anabaena variabilis phenylalanine [Phe] ammonia lyase [PAL] conjugated with polyethylene glycol [PEG]) treatment in adults with phenylketonuria (PKU) and its impact on safety and efficacy.
Methods: Immunogenicity was assessed during induction, upward titration, and maintenance dosing regimens in adults with PKU (n = 261). Total antidrug antibodies (ADA), neutralizing antibodies, immunoglobulin (Ig) M and IgG antibodies against PAL and PEG, IgG and IgM circulating immune complex (CIC) levels, complement components 3 and 4 (C3/C4), plasma Phe, and safety were assessed at baseline and throughout the study.
Background: Weekly rifapentine plus isoniazid for 3 months (3HP) is as effective as daily isoniazid for 9 months (9H) for latent tuberculosis infection in high-risk persons, but there have been reports of possible flu-like syndrome.
Methods: We identified clinically significant systemic drug reactions (SDR) and evaluated risk factors in patients who did not complete treatment in the PREVENT Tuberculosis study.
Results: Among 7552 persons who received ≥ 1 dose of study drug, 153 had a SDR: 138/3893 (3.
Background: Premature discontinuation and poor treatment adherence are problems in chronic conditions, such as multiple sclerosis in which patients must take long-term treatment in order to receive maximum benefit from their medication. The Assessing needs In Multiple Sclerosis (AIMS) study explored factors related to premature treatment discontinuation and patients' experiences of subcutaneous (sc) interferon (IFN) β-1a treatment in the UK.
Methods: A questionnaire-based survey was integrated into the Bupa Home Healthcare patient-support program, which delivers sc IFN β-1a to patients in their home.
Adverse reactions to drugs are common, but only a small percentage of these reactions results from a specific immune reaction to a drug. Over-reactivity of almost any part of the immune system can result in an immunologically mediated drug reaction; however, T cell-and immunoglobulin E-mediated reactions are the most common. The reactions are unpredictable and can involve any part of the body, although skin is most frequent.
View Article and Find Full Text PDFBackground: The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established.
Methods: We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects).
The Sibutramine Cardiovascular Outcomes (SCOUT) trial protocol defines a patient population predominantly outside current European Union label criteria. This article explores responses to sibutramine during the 6-week, single-blind, lead-in period between patients who conformed to the label requirements ("conformers") and those who did not ("nonconformers"). SCOUT is an ongoing, randomized, double-blind, placebo-controlled outcome trial in overweight/obese patients at high risk of a cardiovascular event.
View Article and Find Full Text PDFUncertainties about the cardiovascular safety of sibutramine led to the SCOUT trial that is investigating sibutramine plus weight management in high-risk, overweight/obese patients. A 6-week lead-in period during which all patients received sibutramine permitted an initial assessment of tolerability. A total of 10,742 patients received sibutramine and 3.
View Article and Find Full Text PDFPurpose: To determine if enzyme replacement therapy, involving intravenous infusions of recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme), could be safely continued in patients with Fabry disease who had been withdrawn from a previous clinical trial as a precautionary, protocol-specified measure due to detection of serum IgE antibodies or skin-test reactivity to agalsidase beta.
Methods: The rechallenge infusion protocol specified strict patient monitoring conditions and graded dosing and infusion-rate schemes that were adjusted according to each patient's tolerance to the infusion. Six males (age: 26-66 years) were enrolled.
Aims: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial is a randomized, double-blind comparison of sibutramine vs. placebo, in addition to standard care for weight management, in overweight/obese subjects with an increased risk of cardiovascular disease. The study had an initial single-blind, 6-week lead-in period with sibutramine plus weight management.
View Article and Find Full Text PDFThere is an ever-increasing number of therapeutics used to treat cancer. A recent publication listed 86 currently available antineoplastic medications. Despite this large number, hypersensitivity reactions are not common except with platinum compounds (cisplatin, carboplatin), epipodophyllotoxins (teniposide, etoposide), asparaginase, taxanes (paclitaxel), and procarbazine.
View Article and Find Full Text PDFMost hypersensitivity reactions to drugs occur within several weeks of administration; signs and symptoms are often consistent with known immune-mediated reactions, including anaphylaxis, rashes, fever, cytopenias and vasculitis. The culprit immune mechanisms range from immunoglobulin E antibody to T cells inducing apoptosis of keratinocytes, in the case of bullous exfoliative rashes. Many drugs induce reactions via altered hepatic metabolism, with production of reactive intermediates which induce a common syndrome of rash and fever plus variable types of other signs.
View Article and Find Full Text PDFJ Renin Angiotensin Aldosterone Syst
September 2002
Arterial wall stiffness, an important independent risk factor for cardiovascular disease in patients with hypertension, is worsened by the coexistence of diabetes mellitus. This randomised, prospective, double-blind, crossover trial assessed the effects of telmisartan on arterial stiffness in patients with Type 2 diabetes with essential hypertension. After a two-week placebo wash out period, 28 ambulatory patients received telmisartan (40 mg) or placebo for three weeks.
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