The Impact of Malpractice Damage Caps on C-section Rates and Alternative Approaches.

About half of the states in the United States have had noneconomic damage caps in place for at least 8 years. National aggregate data shows that women are just as likely to give birth by cesarean section (C-section) in states with damage caps as in ones without. For the most recent year studied, the national C-section rate for births in states with damage caps was 33.

The clinical course of patients with idiopathic pulmonary fibrosis.

Background: Prospective data defining the clinical course in idiopathic pulmonary fibrosis (IPF) are sparse.

Objective: To analyze the clinical course of patients with mild to moderate IPF.

Design: Analysis of data from the placebo group of a randomized, controlled trial evaluating interferon-gamma1b.

High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis.

Rationale: High-resolution computed tomography (HRCT) is an integral aspect of the evaluation of patients with suspected idiopathic pulmonary fibrosis (IPF). However, few studies have evaluated its use in a large cohort.

Objectives: To describe HRCT features in patients with mild to moderate IPF, compare diagnostic evaluations by a radiology core (three thoracic radiologists) with those by study-site radiologists, correlate baseline clinical and physiologic variables with HRCT findings, and evaluate their association with mortality.

Analyses of efficacy end points in a controlled trial of interferon-gamma1b for idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a devastating disease, yet validated, reliable criteria for evaluating patient response to therapies in clinical trials are lacking.

Methods: To optimize selection of end point criteria for the study of interferon (IFN)-gamma1b in patients with IPF, we retrospectively analyzed the components of the primary efficacy end point used in a large, controlled study of 330 patients for reliability, validity, and sensitivity to treatment effect. The primary end point components were death, disease progression defined as a > or = 5 mm Hg increase in resting alveolar-arterial oxygen pressure gradient (P[A-a]O2), and disease progression defined as a > or = 10% decrease in percentage of predicted FVC.

Pharmacokinetics in animals and humans of a first-in-class peptide deformylase inhibitor.

BB-83698, a potent and selective inhibitor of peptide deformylase, was the first compound of this novel antibacterial class to progress to clinical trials. Single- and/or multiple-dose studies with doses ranging from 10 to 50 mg of BB-83698/kg of body weight were done with mice, rats, and dogs. Intravenous pharmacokinetics were characterized by low to moderate clearances and moderate volumes of distribution for all species.

A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients.

We report a randomized, double-blind, multicenter trial in which amphotericin B colloidal dispersion (ABCD [Amphotec]; 6 mg/kg/day) was compared with amphotericin B (AmB; 1.0-1.5 mg/kg/day) for the treatment of invasive aspergillosis in 174 patients.

Phase i/ii trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus-infected adults.

Tenofovir DF is an antiviral nucleotide with activity against human immunodeficiency virus type 1 (HIV-1). The pharmacokinetics, safety, and activity of oral tenofovir DF in HIV-1-infected adults were evaluated in a randomized, double-blind, placebo-controlled, escalating-dose study of four doses (75, 150, 300, and 600 mg given once daily). Subjects received a single dose of tenofovir DF or a placebo, followed by a 7-day washout period.

Clinical uses of cidofovir.

Cidofovir is a cytidine nucleotide analogue recently licensed as an intravenous treatment for CMV retinitis in AIDS patients. Three controlled clinical trials have demonstrated efficacy of cidofovir for this indication, and have generated data useful as a guideline to prevent potential toxicity. Although de novo emergence of resistance to cidofovir has not been observed clinically in patients receiving cidofovir, cross-resistance to cidofovir in ganciclovir-resistant clinical DNA polymerase mutants has been identified.

Phase I study of combination therapy with intravenous cidofovir and oral ganciclovir for cytomegalovirus retinitis in patients with AIDS.

Ganciclovir and cidofovir, two antiviral agents used in the treatment of cytomegalovirus (CMV) retinitis, have a synergistic effect inhibiting CMV replication in vitro. In a phase I study, seven patients with AIDS-related CMV retinitis were treated with cidofovir (5 mg/kg intravenously every 2 weeks) combined with ganciclovir (1 g orally three times a day). During a median of 5.

A multicenter phase I/II dose escalation study of single-dose cidofovir gel for treatment of recurrent genital herpes.

A randomized, double-blind, clinic-initiated, sequential dose-escalation pilot study was performed to compare the safety and efficacy of single applications of 1, 3, and 5% cidofovir gel with placebo in the treatment of early, lesional, recurrent genital herpes at five Canadian outpatient sites. Ninety-six patients began treatment within 12 h of lesion appearance and were evaluated twice daily until healing of the lesion occurred. Cidofovir gel at all strengths significantly decreased the median time to negative virus culture in a dose-dependent fashion (3.

Safety, pharmacokinetics, and antiretroviral activity of intravenous 9-[2-(R)-(Phosphonomethoxy)propyl]adenine, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults.

9-[2-(R)-(Phosphonomethoxy)propyl]adenine (PMPA) is a nucleotide analogue with potent antiretroviral activity in vitro and in simian models. A randomized, double-blind, placebo-controlled, dose-escalation clinical trial of intravenous PMPA monotherapy was conducted in 20 human immunodeficiency virus (HIV)-infected adults with CD4 cell counts of >/=200 cells/mm3 and plasma HIV RNA levels of >/=10,000 copies/ml. Two dose levels were evaluated (1 and 3 mg/kg of body weight/day).

Chronic vulvar ulceration in an immunocompetent woman due to acyclovir-resistant, thymidine kinase-deficient herpes simplex virus.

A 34-year-old healthy woman presented with a 15-month history of persistent, nonhealing vulvar ulcerations due to herpes simplex virus (HSV) type 2. Extensive dermatologic workup and serial skin biopsies failed to reveal an underlying vulvar dermatosis or autoimmune bullous disorder. Virologic studies revealed resistance to acyclovir in vitro due to deficiency in thymidine kinase activity.

Association between Cryptosporidium infection and animal exposure in HIV-infected individuals.

Cryptosporidium causes a debilitating illness in immunocompromised individuals, yet the source of sporadic Cryptosporidium infections is unknown. Because early cases of cryptosporidiosis were associated with animals, and pets are a source of companionship to individuals with AIDS, determination of the risk of cryptosporidiosis associated with pets is important. To assess this risk, we conducted a case-control study of HIV-infected individuals with and without cryptosporidiosis.

A randomized, double-blind, placebo-controlled trial of cidofovir gel for the treatment of acyclovir-unresponsive mucocutaneous herpes simplex virus infection in patients with AIDS.

The safety and efficacy of cidofovir gel for treatment of acyclovir-unresponsive herpes simplex virus infections in AIDS patients was evaluated in a randomized, double-blind, multicenter trial. Cidofovir (0.3% or 1%) or placebo gel was applied once daily for 5 days.

Homopolymer mutational hot spots mediate herpes simplex virus resistance to acyclovir.

In the majority of cases, the mechanism underlying the resistance to acyclovir (ACV) of herpes simplex viruses (HSVs) is thymidine kinase (TK) deficiency. Plaque isolates from eight ACV-resistant (ACVr) clinical isolates from AIDS patients, of which five reactivated, were sequenced to determine the genetic lesion within the tk gene conferring resistance and whether this may have correlated with reactivation potential. Mutations were clustered within two homopolymer nucleotide stretches.

Comparison of virus culture and the polymerase chain reaction for diagnosis of mucocutaneous herpes simplex virus infection.

Background And Objectives: The diagnosis of mucocutaneous herpes simplex virus (HSV) is hampered by suboptimal sensitivity of virus culture and atypical clinical morphology.

Goals: To compare the diagnostic usefulness of the polymerase chain reaction (PCR) and virus culture.

Study Design: Consecutive samples from 246 patients at an urban sexually transmitted diseases clinic were tested for HSV by both PCR and virus culture.

Early clinical markers and CD4 percentage in subjects with human immunodeficiency virus infection.

In a clinical trial involving asymptomatic, HIV-seropositive subjects treated with either the HIV-1 immunogen (an inactivated, gp120-depleted HIV-1 virus in incomplete Freund's adjuvant) or an adjuvant control, we examined the relationship between changes in the percentage of CD4 cells over time and early clinical markers of HIV disease progression. Subjects who had an early clinical event were more likely to have a greater decline in the percentage of CD4 cells than those subjects who did not have a clinical event (p = 0.054).

Pilot study of topical trifluridine for the treatment of acyclovir-resistant mucocutaneous herpes simplex disease in patients with AIDS (ACTG 172). AIDS Clinical Trials Group.

Twenty-six AIDS patients were enrolled in an open label pilot study to evaluate the efficacy and toxicity of topical 1 percent ophthalmic trifluridine solution for the treatment of chronic mucocutaneous herpes simplex virus disease unresponsive to at least 10 days of acyclovir therapy. Susceptibility testing to acyclovir, trifluridine, and foscarnet was determined by plaque reduction assay. Twenty-four patients were evaluable for efficacy and 25 for toxicity analyses.

Zidovudine, trimethoprim, and dapsone pharmacokinetic interactions in patients with human immunodeficiency virus infection.

Zidovudine is widely prescribed for the treatment of human immunodeficiency virus (HIV) infection. Trimethoprim and dapsone are commonly used in the management of Pneumocystis carinii pneumonia in HIV-infected patients. To examine the pharmacokinetic interactions among these drugs, eight HIV-infected patients (26 to 43 years old) with a mean CD4 count of 524.

Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group.

Objective: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia.

Design: A randomized, double-blind study.

Setting: 24 U.

Comparative evaluation of microplate enzyme-linked immunosorbent assay versus plaque reduction assay for antiviral susceptibility testing of herpes simplex virus isolates.

We tested the antiviral susceptibilities of 30 clinical isolates of herpes simplex virus using the microplate in situ enzyme-linked immunosorbent assay (MISE) and the plaque reduction assay (PRA). There was concordance for 26 of 30 acyclovir results and all 30 foscarnet results. MISE and PRA results each predicted the response to acyclovir in 12 of 14 instances and the response to foscarnet in 8 instances.