Cost-effectiveness of adrenal vein sampling- vs computed tomography-guided adrenalectomy for unilateral adrenaloma in primary aldosteronism.

PURPOSE: Adrenalectomies performed for the treatment of primary aldosteronism due to unilateral adenoma are traditionally confirmed with, and guided by, results from adrenal vein sampling (AVS). However, the usefulness of AVS at the expense of cost and complications is debated, and many institutions have independent protocols that use AVS to varying degrees. METHODS: Cost-effectiveness of AVS- vs computed tomography (CT)-based adrenalectomy was calculated using decision tree models. The tree was populated with values describing biochemical post-operative outcomes from the published literature; patients were placed into AVS- or CT-dependent treatment arms. Biochemical outcomes were defined based on patients' potassium levels and aldosterone-renin ratios. Patients underwent adrenalectomies and received medical management dosed based on surgical outcomes. Costs were represented by Medicare (FY2021) reimbursement rates (US$) and quality-adjusted life-years (QALYs) were calculated using published morbidity and survival data. A willingness-to-pay of $100,000 per QALY gained was set to determine the most cost-effective strategy. The primary outcome was the incremental cost-effectiveness ratio (ICER) associated with biochemical outcomes. RESULTS: The base case analyses favored the use of AVS-guided care, which cost $307.65 more but yielded 0.78 more QALYs, resulting in an ICER of $392.57. These results were upheld by all one-way and two-way sensitivity analyses. In 100,000 random-sampling simulations, AVS-guided care was favored 100% of the time. CONCLUSIONS: For patients with primary aldosteronism receiving adrenalectomies with curative intent, the more cost-effective method based on biochemical outcomes is AVS-based care. Recent literature suggests biochemical resolution should be favored over clinical resolution, due to long-term detriments of increased aldosterone independent of clinical symptoms.

Mechanisms controlling theophylline release from ethanol-resistant coated pellets.

PURPOSE: To elucidate the mass transport mechanisms controlling drug release from recently proposed, ethanol-resistant, polymeric film coatings. METHODS: Theophylline matrix pellets were coated with ethylcellulose: guar gum blends. Drug release from single pellets and ensembles of pellets was measured in various release media. Changes in the systems' morphology, composition and mechanical properties were monitored using SEM, gravimetrical analysis and a texture analyzer. Based on the obtained experimental results a mechanistically realistic mathematical model was identified and used to quantitatively predict drug release from coated pellets in ethanol-free and ethanol-containing bulk fluids. RESULTS: Drug diffusion though the intact polymeric film coatings is likely to be the dominant mass transport mechanism in the investigated systems, irrespective of the ethanol content in the surrounding environment. An appropriate solution of Fick's law could be used to quantitatively predict theophylline release from pellets coated with different ethylcellulose:guar gum blends at different coating levels. Importantly, independent experiments confirmed the theoretical predictions. CONCLUSIONS: In silico simulations can help facilitating the optimization of the novel ethanol-resistant polymeric film coatings, avoiding time-consuming and cost-intensive series of trial-and-error experiments. The presence/absence of ethanol does not affect the underlying drug release mechanisms.

Ethanol-resistant ethylcellulose/guar gum coatings--importance of formulation parameters.

Recently, ethylcellulose/guar gum blends have been reported to provide ethanol-resistant drug release kinetics from coated dosage forms. This is because the ethanol insoluble guar gum effectively avoids undesired ethylcellulose dissolution in ethanol-rich bulk fluids. However, so far the importance of crucial formulation parameters, including the minimum amount of guar gum to be incorporated and the minimum required guar gum viscosity, remains unclear. The aim of this study was to identify the most important film coating properties, determining whether or not the resulting drug release kinetics is ethanol-resistant. Theophylline matrix cores were coated in a fluid bed with blends of the aqueous ethylcellulose dispersion "Aquacoat®ECD30" and guar gum. The polymer blend ratio, guar gum viscosity, and degree of dilution of the final coating dispersion were varied. Importantly, it was found that more than 5% guar gum (referred to the total polymer content) must be incorporated in the film coating and that the apparent viscosity of a 1% aqueous guar gum solution must be greater than 150 cP to provide ethanol-resistance. In contrast, the investigated degree of coating dispersion dilution was not found to be decisive for the ethanol sensitivity. Furthermore, all investigated formulations were long term stable, even upon open storage under stress conditions for 6 months.

Ethanol-resistant polymeric film coatings for controlled drug delivery.

The sensitivity of controlled release dosage forms to the presence of ethanol in the gastro intestinal tract is critical, if the incorporated drug is potent and exhibits severe side effects. This is for instance the case for most opioid drugs. The co-ingestion of alcoholic beverages can lead to dose dumping and potentially fatal consequences. For these reasons the marketing of hydromorphone HCl extended release capsules (Palladone) was suspended. The aim of this study was to develop a novel type of controlled release film coatings, which are ethanol-resistant: even the presence of high ethanol concentrations in the surrounding bulk fluid (e.g., up to 40%) should not affect the resulting drug release kinetics. Interestingly, blends of ethylcellulose and medium or high viscosity guar gums provide such ethanol resistance. Theophylline release from pellets coated with the aqueous ethylcellulose dispersion Aquacoat® ECD 30 containing 10 or 15% medium and high viscosity guar gum was virtually unaffected by the addition of 40% ethanol to the release medium. Furthermore, drug release was shown to be long term stable from this type of dosage forms under ambient and stress conditions (without packaging material), upon appropriate curing.

Monotherapy versus combination antibiotic therapy for patients with bacteremic Streptococcus pneumoniae community-acquired pneumonia.

The purpose of this study was to examine the impact of antimicrobial monotherapy vs combination therapy on length of stay and mortality for patients with Streptococcus pneumoniae pneumonia. Thirty-nine percent of patients received monotherapy, while 61% received combination therapy. Although there was no significant difference in mortality (OR 1.25, 95% CI = 0.25-6.8), there was a significant increase in length of stay for patients who received combination therapy (p = 0.02). Patients with bacteremic pneumococcal pneumonia treated with empiric combination therapy had no significant difference in mortality; however, they did have increased length of stay after adjusting for severity of illness. Randomized controlled trials are needed to determine what is the optimal empiric antimicrobial regime for patients with community-acquired pneumonia.

Acute abdomen secondary to ascaris lumbricoides infestation of the small bowel.

Ascariasis is a helminthic infection commonly found in tropical climates. It often propagates in communities of low socioeconomic status secondary to contamination of the soil and water supply with human feces. We present a case report of a 42-year-old Asian-Indian female presenting with a long-standing history of severe recurrent postprandial epigastric pain, requiring multiple hospital admissions. Ultrasound, computed tomography (CT), and nuclear biliary scan were negative. She underwent esophagogastroduodenoscopy that suggested ischemia. Magnetic resonance angiography (MRA) and mesenteric angiography were inconclusive. As conservative treatment had been unsuccessful, a small bowel series was performed. The radiographs demonstrated characteristic findings of Ascaris lumbricoides infestation. Although the prevalence, diagnosis, and subsequent treatment of an acute abdomen secondary to Ascaris lumbricoides infestation is commonly seen in developing countries, clinicians in developed countries may not consider this entity when faced with a patient with similar symptoms. We frequently care for immigrants from developing countries and our own citizens who visit the countries where ascariasis is endemic. Therefore, heightened awareness of Ascaris lumbricoides infection (ALI) presenting as an acute abdomen is necessary. The diagnosis requires an experienced radiologist and knowledge by the clinician of treatment options and of when a surgeon should be involved.

Effects of moderate and high doses of alcohol on attention, impulsivity, discriminability, and response bias in immediate and delayed memory task performance.

BACKGROUND: Prior studies that examined the effects of alcohol on Continuous Performance Test (CPT) performance have resulted in inconsistent outcomes. Most studies that examined the effects of alcohol on concentrated attention tasks (like the CPT) found little effect of alcohol on performance measures, even when doses that exceeded 0.8 g/kg were used. One likely reason for these inconsistencies is the varying difficulty (and sensitivity) of the task used, and as a result, comparisons between studies are difficult. This study is one in a series that examines the effects of alcohol on attention by using a difficult version of the CPT (Immediate and Delayed Memory Task--IMT/DMT). Our purpose for these studies has been two-fold, examining the effects of alcohol (1) on concentrated attention (i.e., correct detections) and (2) on errors (i.e., commission errors) previously correlated with impulsive behaviors. The first is important because previous studies have shown little effect of alcohol on attention, and the second is important because commission errors have been related to impulsive behaviors. METHODS: In the IMT/DMT, participants respond to a briefly displayed number when it is identical to the one displayed before it. The procedure includes immediate and delayed conditions where successive stimuli to be matched are delayed by 0.5 sec or by 3.5 sec. The three stimulus types included target (identical match), catch (four of five digits match), and filler (no match) stimuli. Twenty subjects completed this task after consuming either a placebo drink or a drink that contained 0.5 g/kg or 1.0 g/kg of alcohol on different days. RESULTS: The main findings were that (1) alcohol decreased the percentage of correct identifications of target stimuli; (2) alcohol increased the percentage of commission errors in relation to the number of correct target responses; and (3) alcohol decreased discriminability whereas response bias became more conservative. CONCLUSIONS: These results clearly demonstrated a time-course effect of the 1.0 g/kg alcohol dose on attention, impulsivity, discrimination, and response criteria when a variety of dependent measures are used.

Partial characterization of the proteolytic secretions of Acanthamoeba polyphaga.

The ocular pathology associated with acanthamoebiasis may result, at least in part, from the excretory and secretory (E&S) products of the active Acanthamoeba trophozoites. To test this hypothesis, the ability of A. polyphaga (ATCC Strain 30461) trophozoite E&S products to digest collagen, the major constituent of the corneal stroma, was evaluated. The secreted proteinases of A. polyphaga were identified using in vitro azocoll degradation, activity-PAGE, radiolabeled extracellular matrix (ECM) degradation, and collagen degradation assays. Inhibitors of serine (phenylmethylsulfonyl fluoride, diisopropyl fluorophosphate), cysteine [benzyloxyphenylalanyl-analyl fluoromethyl ketone, N-ethylmaleamide, ethylenediamine tetraacetic acid (EDTA), L-trans-3-carboxyiran-2-carbonyl-L-leucylagmatine], metallo- (1,10-phenanthroline, EDTA, phosphoramidon), and aspartyl (pepstatin A) proteinases were incorporated into the assays. Proteinase activity was detected in trophozoites and the E&S products of trophozoites but not in cysts. The azocoll and activity-PAGE assays indicated the presence of serine and cysteine proteinases, while degradation of the radiolabeled ECM by live trophozoites confirmed not only the presence of serine and cysteine proteinases but also metalloproteinase(s). Most proteinase activity occurred at neutral pH. Incubation of E&S with type I collagen did not yield the typical 3/4:1/4 products characteristic of vertebrate collagenases. These data suggest that E&S products of A. polyphaga contain multiple serine and cysteine proteinases with nonspecific collagenolytic activity and that metallproteinases form an additional minor constituent.

Pulmonary function and morbidity in textile mill workers.

The study was conducted in a large cotton textile mill in Surat City. A selected number of 278 employees were evaluated for social, anthropological and pulmonary functions. No parameters except the period of exposure to dust reduced pulmonary function; it was statistically significant in the case of vital capacity and maximum breathing capacity. Out of 23.94% pulmonary morbidity observed, the byssinosis rate was 1.62.