Training received by teachers of students with autism spectrum disorders (ASD) in one southern state was investigated. Teachers (n 90) reported training received via an online version of the Autism Treatment Survey. The most common type of training reported was attendance at a full- or half-day workshop; fewer than 15% reported receiving training from teacher preparation programs at colleges or universities. The types of training received did not predict the use of evidence-based practices. Individual factors related to training were not significant for education level, years of teaching students with ASD, and type of class (i.e., general or special education). The need for an increased role for personnel preparation programs for teachers of students with ASD is discussed.
Background and objectives: Calcification of the mitral and aortic valves is common in dialysis patients (CKD-5D). However, the prognostic significance of valvular calcification (VC) in CKD is not well established.
Design, setting, participants, & measurements: 144 adult CKD-5D patients underwent bidimensional echocardiography for qualitative assessment of VC and cardiac computed tomography (CT) for quantification of coronary artery calcium (CAC) and VC. The patients were followed for a median of 5.6 years for mortality from all causes.
Results: Overall, 38.2% of patients had mitral VC and 44.4% had aortic VC on echocardiography. Patients with VC were older and less likely to be African American; all other characteristics were similar between groups. The mortality rate of patients with calcification of either valve was higher than for patients without VC. After adjustment for age, gender, race, diabetes mellitus, and history of atherosclerotic disease, only mitral VC remained independently associated with all-cause mortality (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.03 to 2.91). Patients with calcification of both valves had a two-fold increased risk of death during follow-up compared with patients without VC (HR, 2.16; 95% CI, 1.14 to 4.08). A combined CT score of VC and CAC was strongly associated with all-cause mortality during follow-up (HR for highest versus lowest tertile, 2.21; 95% CI, 1.08 to 4.54).
Conclusions: VC is associated with a significantly increased risk for all-cause mortality in CKD-5D patients. These findings support the use of echocardiography for risk stratification in CKD-5D as recently suggested in the Kidney Disease Improving Global Outcomes guidelines.
In recent years, evidence has accumulated indicating that the enzyme arginase, which converts L-arginine into L-ornithine and urea, plays a key role in the pathogenesis of pulmonary disorders such as asthma through dysregulation of L-arginine metabolism and modulation of nitric oxide (NO) homeostasis. Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Through substrate competition, arginase decreases bioavailability of L-arginine for nitric oxide synthase (NOS), thereby limiting NO production with subsequent effects on airway tone and inflammation. By decreasing L-arginine bioavailability, arginase may also contribute to the uncoupling of NOS and the formation of the proinflammatory oxidant peroxynitrite in the airways. Finally, arginase may play a role in the development of chronic airway remodeling through formation of L-ornithine with downstream production of polyamines and L-proline, which are involved in processes of cellular proliferation and collagen deposition. Further research on modulation of arginase activity and L-arginine bioavailability may reveal promising novel therapeutic strategies for asthma.
Rationale: Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability. Objectives: To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI). Methods: We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of "no treatment" used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms. Results: Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen. Conclusions: Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced, study designers should consider relaxing non-inferiority boundaries.
Objective: To compare the effectiveness of ondansetron and prochlorperazine to treat vomiting. Secondary objectives were the effectiveness of ondansetron and prochlorperazine to treat nausea and their tolerability. Methods: This was a prospective, randomized, active controlled, double-blinded study. Using a convenience sample, patients were randomized to either intravenous ondansetron 4mg (n=32) or prochlorperazine 10mg (n=32). The primary outcome was the percentage of patients with vomiting at 0-30, 31-60, and 61-120 minutes after the administration of ondansetron or prochlorperazine. Secondary outcomes were nausea assessed by a visual analog scale (VAS) at baseline, 0-30, 31-60, and 61-120 minutes after the administration of ondansetron or prochlorperazine and the percentage of patients with adverse effects (sedation, headache, akathisia, dystonia) to either drug. We performed statistical analyses on the VAS scales at each time point and did a subgroup analysis to examine if nausea scores were affected if the patient had vomited at baseline. Results: The primary identified cause for nausea and vomiting was flu-like illness or gastroenteritis (19%). The number of patients experiencing breakthrough vomiting at 0-30, 31-60, and 61-120 minutes was similar between groups for these time periods; however, more patients receiving ondansetron experienced vomiting overall (7 [22%] vs. 2[3.2%] patients, p=not significant). Nausea scores at baseline and 0-30 minutes were severe and similar between groups; however, at 31-60 and 61-120 minutes, patients receiving prochlorperazine had better control of nausea (24.9 vs. 43.7 mm, p=0.03; 16.8 vs. 34.3 mm, p=0.05). Sedation scores were similar between groups. There were no cases of extrapyramidal symptoms as assessed by the treating physician and there were four cases of akathisia (prochlorperazine=3 [9%], ondansetron=1[3%] ). Conclusion: Prochlorperazine and ondansetron appear to be equally effective at treating vomiting in the emergency department.
Background
Aminoglycoside ototoxicity is one of the common health problems. Mitochondrial 12S rRNA mutations are one of the important causes of aminoglycoside ototoxicity. However, the incidences of 12S rRNA mutations associated with aminoglycoside ototoxicity are less known.
Methods
A total of 440 Chinese pediatric hearing-impaired subjects were recruited from two otology clinics in the Ningbo and Wenzhou cities of Zhejiang Province, China. These subjects underwent clinical, genetic evaluation and molecular analysis of mitochondrial 12S rRNA. Resultant mtDNA variants were evaluated by structural and phylogenetic analysis.
Results
The study samples consisted of 227 males and 213 females. The age of all participants ranged from 1 years old to 18 years, with the median age of 9 years. Ninety-eight subjects (58 males and 40 females) had a history of exposure to aminoglycosides, accounting for 22.3% cases of hearing loss in this cohort. Molecular analysis of 12S rRNA gene identified 41 (39 known and 2 novel) variants. The incidences of the known deafness-associated 1555A > G, 1494C > T and 1095T > C mutations were 7.5%, 0.45% and 0.91% in this entire hearing-impaired subjects, respectively, and 21.4%, 2% and 2% among 98 subjects with aminoglycoside ototoxicity, respectively. The structural and phylogenetic evaluations showed that a novel 747A > G variant and known 839A > G, 1027A > G, 1310C > T and 1413T > C variants conferred increased sensitivity to aminoglycosides or nonsyndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this rRNA. However, other variants were polymorphisms. Of 44 subjects carrying one of definite or putative deafness-related 12S rRNA variants, only one subject carrying the 1413T > C variant harbored the 235DelC/299DelAT mutations in the GJB2 gene, while none of mutations in GJB2 gene was detected in other 43 subjects.
Conclusions
Mutations in mitochondrial 12S rRNA accounted for ~30% cases of aminoglycoside-induced deafness in this cohort. Our data strongly support the idea that the mitochondrial 12S rRNA is the hot spot for mutations associated with aminoglycoside ototoxicity. These data have been providing valuable information and technology to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside antibiotic therapy, and eventually to decrease the incidence of deafness.
Go to:
Testis cancer is one of the few solid organ malignancies for which reliable serum tumor markers are available to help guide disease management. Human chorionic gonadotropin, alpha fetoprotein, and lactate dehydrogenase play crucial roles in diagnosis, staging, prognosis, monitoring treatment response, and surveillance of seminomatous and nonseminomatous germ cell tumors. Herein we discuss the clinical applications of germ cell tumor markers, the limitations of these markers in the management of this disease, and additional serum molecules that have been identified with potential roles as novel germ cell tumor markers.
Introduction: Poisoning is an increasingly important cause of injury in the United States. In 2009 poison centers received 2,479,355 exposure reports, underscoring the role of poison centers in intentional and unintentional injury prevention. Antiretroviral (ARV) agents are commonly prescribed drugs known to cause toxicity, yet the frequency of these incidents is unknown. The objectives of this study were to quantify the number of reported cases of toxicity secondary to ARV agents at a regional poison center, and to describe the circumstances and clinical manifestations of these poisonings. Methods: We conducted a retrospective review of poison center records between December 1, 2001, and January 7, 2010. Results: One hundred sixty-two exposures to ARV agents were reported to the poison center, of which 30% were intentional and 70% were unintentional. Three patients developed major toxicity and no deaths occurred. The remaining patients developed moderate and minor effects as defined by poison center guidelines. Conclusion: ARV drug toxicity appears to be infrequently reported to the poison center. Fatal and major toxicities are uncommon, and intentional overdoses are associated with a more serious toxicity. Educational efforts should encourage clinicians to report toxicities related to the use of ARV agents to poison centers in order to better study this problem.
Tetrahydrobiopterin (BH4) responsiveness is currently defined as a decrease in plasma phenylalanine concentrations in patients with phenylketonuria (PKU). This definition does not offer insight beyond the initial assessment of patients, which may lead to treatment ambiguity in patients who only experience an initial decrease in plasma phenylalanine concentrations. We present our experience with a novel classification approach using sequentially-applied criteria. Plasma phenylalanine concentrations were measured at baseline and after one month of BH4 therapy (20 mg/kg/day) in 58 PKU patients (34M, 24F; age 17.3 ± 11.0 years). Thirty-two patients (55.2%) were classified as –preliminary responders“ at one month, experiencing at least a 15% decrease in plasma phenylalanine concentrations. Preliminary responders’ ability to liberalize their dietary restrictions was then systematically assessed. –Definitive responders“ were defined as preliminary responders who could increase their dietary phenylalanine tolerance by at least 300 mg/day and lower prescribed medical food needs by at least 25% while maintaining metabolic control (plasma phenylalanine <360 μmol/L) and consuming adequate dietary protein. Preliminary responders who could not liberalize their diets according to these criteria were classified as –provisional responders.“ Nineteen patients (32.8% of patients initiating BH4 therapy) met the definitive responder criteria, increasing dietary phenylalanine tolerance from 704 ± 518 mg/day to 1922 ± 612 mg/day and reducing medical food to 16.7 ±19.5% of their baseline prescription. Nine patients (15.5% of patients initiating BH4 therapy) were classified as provisional responders, all remaining on 100% of their baseline medical food prescription. From this classification approach, a subgroup of provisionally responsive patients emerged who experienced an initial decrease in plasma phenylalanine concentrations but who could not substantially increase their dietary phenylalanine tolerance or decrease medical food needs. Diet liberalization is an essential component of BH4-responsiveness classification.
In recent years, evidence has increased that asthma predisposes to complications of sickle cell disease (SCD), such as pain crises, acute chest syndrome, pulmonary hypertension, and stroke, and is associated with increased mortality. An obstructive pattern of pulmonary function, along with a higher-than-expected prevalence of airway hyper-responsiveness (AHR) when compared to the general population, has led some researchers to suspect that underlying hemolysis may contribute to the development of a pulmonary disease similar to asthma in patients with SCD. While the pathophysiologic mechanism in atopic asthma involves up-regulation of Th2 cytokines, mast cell- and eosinophil-driven inflammation, plus increased activity of inducible nitric oxide synthase (iNOS) and arginase in airway epithelium resulting in obstructive changes and AHR, the exact mechanisms of AHR, obstructive and restrictive lung disease in SCD is unclear. It is known that SCD is associated with a proinflammatory state and an enhanced inflammatory response is seen during vaso-occlusive events (VOE). Hemolysis-driven acute-on-chronic inflammation and dysregulated arginine-nitric oxide metabolism are potential mechanisms by which pulmonary dysfunction could occur in patients with SCD. In patients with a genetic predisposition of atopic asthma, these changes are probably more severe and result in increased susceptibility to sickle cell complications. Early recognition and aggressive management of asthma based on established National Institutes of Health asthma guidelines is recommended in order to minimize morbidity and mortality.