Since 1968 the number of reported cases of allergic bronchopulmonary aspergillosis in the United States has risen secondary to increased awareness by physicians and to improved diagnostic criteria for identifying the disease. The eight diagnostic criteria, the five clinical stages of the disease, the common radiographic changes, the pathologic findings, the common laboratory findings, the possible pathogenetic mechanisms involved, the differential diagnosis, the acute and chronic pulmonary function changes, and the importance of corticosteroid therapy in treatment of exacerbations and prevention of further lung damage are reviewed.
Approximately 60% of women in the United States experience a UTI, or acute cystitis, during their lifetime. Of these, 30% go on to have multiple recurrences.1 For women who suffer from frequent recurrences, effective preventive strategies are essential to free them from this disruptive illness. Unfortunately, the use of antibiotics for UTI prevention is becoming more problematic because resistance to commonly used agents is now widespread, infection caused by Clostridium difficile is increasingly common, and our appreciation of the importance of an undisturbed microbiome in health is growing. Therefore, investigations of antibiotic-sparing approaches to UTI prevention are of great interest to physicians and patients alike.
Accepted for Publication: March 3, 2012. Author Affiliations: Division of Geriatric Medicine and Gerontology, School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland. Correspondence: Dr Finucane, Division of Geriatric Medicine and Gerontology, School of Medicine, Johns Hopkins Bayview Medical Center, 5505 Hopkins Bayview Cir, John R. Burton Pavilion, 01 Terrace, Baltimore, MD 21224 (tfinucan@jhmi.edu). Financial Disclosure: None reported. REFERENCES
I n 2007, President George W. Bush signed into law the Food and Drug Administration Amendments Act (FDAAA) (121 Stat 962). This Act, by adding subsection (k)(5) to section 505 (21 USC §355), directed the Food and Drug Administration (FDA) to “conduct regular, bi-weekly screening of the Adverse Event Reporting System [AERS] database and post a quarterly report on the AERS Website of any new safety information or potential signal of a serious risk identified by AERS within the last quarter.” The AERS contains over 4 million reported adverse events data from 1969 until the pres-
In light of the predictions of two competing approaches to adult L2 acquisition – Full Access (FA) (e.g., White 1989, 2003; Schwartz & Sprouse 1996) and Failed Features (FF) (e.g., Hawkins & Chan 1997; Liceras & Díaz, 1999) – the present study examines the acquisition of inflected infinitives by English and Spanish/English bilingual adult learners of L2 Portuguese. Target-like acquisition of inflected infinitives requires the resetting of both a syntactic parameter (the Null Subject Parameter) and a morphological parameter (the Infl-parameter) for these learners. Since FF approaches maintain a post-critical period failure to acquire new L2 features lacking from the L1, target-like acquisition is predicted to not be possible. Conversely, FA approaches, which maintain adult parameter resetting is possible, predict that native-like competence of inflected infinitives is attainable, but not inevitably so. The data we present support FA approaches, demonstrating that advanced adult learners achieve native-like interpretative knowledge of Portuguese inflected infinitives. We also consider the role of L1 transfer and its possible implications, as they differ for both groups. * We would like to thank Carlos Quicoli and Acrisio Pires for their help and insightful comments. We also thank the audiences at Second Language Research Forum 2006, the Hispanic Linguistic Symposium 2006 and the Hispanic Linguistic colloquium at the University of Iowa for helpful comments, especially Silvina Montrul, Liliana Sánchez, Maria Fruit and Paula Kempchinsky. We wish to express our most sincere gratitude to María Jose Barbosa, Brett Johnson and everyone at the Acebeu for their gracious help facilitating the collection of data in Salvador, Brazil. This article benefited greatly from the suggestions of the anonymous reviewers as well as the editorial expertise of Brian Krechman and Andrew Carter. The normal disclaimers apply. 4 Jason Rothman & Michael Iverson
BACKGROUND Obese individuals who have failed to achieve adequate weight loss with lifestyle changes have limited nonsurgical therapeutic options. We evaluated the efficacy and tolerability of zonisamide, an antiepileptic drug, for enhancing weight loss in obese patients receiving diet and lifestyle guidance. METHODS This was a 1-year, randomized, double-blind, placebo-controlled trial conducted from January 9, 2006, through September 20, 2011, at Duke University Medical Center. A total of 225 obese (mean [SD] body mass index, 37.6 [4.9]) participants included 134 women (59.6%) and 91 men (40.4%) without diabetes mellitus. (Body mass index is calculated as weight in kilograms divided by height in meters squared.) Interventions were daily dosing with placebo (n = 74), 200 mg of zonisamide (n = 76), or 400 mg of zonisamide (n = 75), in addition to diet and lifestyle counseling by a dietitian for 1 year. Primary outcome was change in body weight at 1 year. RESULTS Of the 225 randomized patients, 218 (96.9%) provided 1-year follow-up assessments. Change in body weight was -4.0 kg (95% CI, -5.8 to -2.3 kg; least squares mean, -3.7%) for placebo, -4.4 kg (-6.1 to -2.6 kg; -3.9%; P = .79 vs placebo) for 200 mg of zonisamide, and -7.3 kg (-9.0 to -5.6 kg; -6.8%; P = .009 vs placebo) for 400 mg of zonisamide. In the categorical analysis, 23 (31.1%) assigned to placebo, 26 (34.2%; P = .72) assigned to 200 mg of zonisamide, and 41 (54.7%; P = .007) assigned to 400 mg of zonisamide achieved 5% or greater weight loss; for 10% or greater weight loss, the corresponding numbers were 6 (8.1%), 17 (22.4%; P = .02), and 24 (32.0%; P < .001). Gastrointestinal, nervous system, and psychiatric adverse events occurred at a higher incidence with zonisamide than with placebo. CONCLUSION Zonisamide at the daily dose of 400 mg moderately enhanced weight loss achieved with diet and lifestyle counseling but had a high incidence of adverse events. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00275834
BACKGROUND:There is interest in whether a short course of combination antiretroviral therapy (cART) at the time of human immunodeficiency virus (HIV) seroconversion could induce long-term immunologic control after its interruption. We aimed to determine the time of virologic rebound after interruption of treatment initiated close to HIV seroconversion and to identify potential cases of posttreatment controllers (PTCs) in the CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe) Collaboration. METHODS:Prospective cohort study nested within the CASCADE database of routinely collected data about patients with HIV with well-estimated date of HIV seroconversion from Europe, Canada, and Australia in the post-cART era. Participants were individuals who interrupted successful cART initiated within 3 months of HIV seroconversion. The main outcome was loss of PTC status, defined as the earlier date of virologic rebound (first of 2 consecutive measurements showing HIV RNA levels >50 copies/mL) or reinitiation of any ART after cART interruption. RESULTS:Median time to loss of PTC status in 259 eligible individuals was 1.7 months. Eleven patients did not experience virologic rebound by 24 months after treatment interruption. CONCLUSION:Most patients experience virologic rebound soon after cART interruption; however, although PTCs are rare, the results of this study confirm their existence.
A ir pollution is a pervasive consequence of modern societies. Beyond being an environmental hazard, several pollutants such as particulate matter (PM) pose significant health threats. Fine PM ( 2.5 μm in diameter; PM2.5) is a heterogeneous mixture of compounds (eg, carbon, sulfates, nitrates, and metals) principally derived from the combustion of fossil fuels. Given the billions of people exposed, the adverse effects of PM represent a major global health epidemic. Although adverse pulmonary responses may be the most conspicuous effects of PM, in actuality, cardiovascular (CV) diseases account for the largest proportion of the PM-related public health burden. Exposures to ambient PM2.5 over both the short and long term have been associated with a variety of CV events. The epidemiologic evidence and the mechanistic bases for such an association have grown substantively. In this context, the American Heart Association recently published an updated scientific statement concluding that PM2.5 is an important modifiable factor contributing to CV diseases. Over the past decade, several (but not all) studies have also demonstrated a linkage between air pollutants (including PM) and stroke. This putative relationship has enormous public health ramifications, since stroke is the second leading cause of death worldwide. Moreover, lowto middle-income countries that are subject to severe air pollution problems also bear a disproportionate burden of global stroke mortality. Though the immediate risks posed by air pollution to any single individual may be small, the population-attributable risk for stroke is highly significant, given the pervasive nature of the problem. For example, while PM exposure increases myocardial infarction risk by only 1% to 2% within days, owing to the enormous number of individuals continuously exposed, it can account for the instigation of up to 4% of all events in a population. In addition, air pollutants have been shown to adversely modulate several of the traditional CV risk factors (such as blood pressure), which altogether account for roughly 90% of all strokes worldwide. In this issue of the Archives, an article by Wellenius et al provides some important information that helps to further elucidate the relationship between air pollutants and stroke. In a study of patients admitted to a stroke center in Boston, the authors found that the risk for ischemic stroke was elevated acutely following shortterm exposure to higher levels of ambient PM2.5. Hemorrhagic strokes were not investigated; however, this subtype has been less consistently associated with stroke in the past. Although this single-center study was smaller than some prior studies, there are several unique aspects. Fine particulate matter, black carbon, and nitrogen dioxide were associated with ischemic stroke, but ozone or sulfates were not, suggesting a major contribution of traffic-related particulates. These positive associations were also shown to persist when PM2.5 levels were well below current daily ambient air quality standards ( 35 μg/m), suggesting that more aggressive regulations are required to lower risk among all susceptible people. The risks for ischemic stroke subtypes were also well characterized and shown to be related to largeartery and small-vessel events but not cardioembolic events. Perhaps most noteworthy among their findings was the importance of very recent PM2.5 exposures over the preceding 6 to 24 hours for triggering an event. Though several studies have found positive relationships with same-day or previous-days pollution levels, none has investigated the degree of temporal resolution provided by this analyses. The extremely rapid increase in stroke risk is an important novel insight; however, it should be noted that the temporal nature of PMmediated CV events is a complex issue that has been controversial of late. Why are these findings important? Current US and World Health Organization air quality standards focus only on daily and annual PM2.5 mean concentrations. There is no biological basis that these specific durations of exposure are required to instigate strokes or other CV events. These temporal windows have typically been chosen owing to limitations of available air pollution data and because longer averaging periods were thought to provide more reliable exposure estimates. The findings by Wellenius et al remind us that clinical events could be initiated by even briefer subdaily periods of PM2.5 inhalation. Indeed, controlled-exposure studies and panel studies corroborate this possibility showing that adverse biological responses can occur within hours. With the availability of improving pollutant data, future studies should aim to elucidate the health effects of subdaily time windows of exposure. If similar findings are corroborated and/or found for other diseases, those who create air quality standards might need to consider the difficult task of curbing subdaily
